{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:42:28Z","timestamp":1759970548459,"version":"build-2065373602"},"reference-count":82,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Computation"],"abstract":"<jats:p>SLITRK1 is a critical protein involved in neural development and is associated with various neurological disorders, including Tourette Syndrome. This study investigates the structural dynamics, intrinsic disorder propensity, and pharmacological interactions of SLITRK1, with a particular focus on amino acid substitutions and their pathological implications. A comprehensive computational framework was employed, including intrinsic disorder region analysis, transmembrane topology predictions, and stability assessments of SLITRK1 variants. Integrated with reinforcement learning (RL), molecular docking and dynamics simulations were used to evaluate the pharmacotherapeutic potential of drugs commonly prescribed for Tourette Syndrome, such as Pimozide, Aripiprazole, Risperidone, and Haloperidol. Structural analyses revealed that the S656M mutation significantly alters SLITRK1\u2019s 3D conformation, biological functions, and drug binding profiles. Among the tested drugs, Aripiprazole exhibited the highest binding affinity across various SLITRK1 variants, with reinforcement learning highlighting a notable interaction with the S659K mutation. These findings were supported by Ramachandran plot and molecular dynamics analyses, which identified mutation-induced structural and dynamic changes. This study provides an integrative analysis of SLITRK1, offering insights into its role in Tourette Syndrome and laying a foundation for targeted therapeutic strategies to mitigate SLITRK1-related neurological disorders.<\/jats:p>","DOI":"10.3390\/computation13020029","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T09:42:23Z","timestamp":1737970943000},"page":"29","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioinformatics-Driven Structural and Pharmacological Analysis of SLITRK1 in Tourette Syndrome: Impact of S656M Mutation Using Molecular Dynamics, Docking, and Reinforcement Learning"],"prefix":"10.3390","volume":"13","author":[{"given":"Emre","family":"Akta\u015f","sequence":"first","affiliation":[{"name":"Faculty of Art and Science, Molecular Biology and Genetics, Y\u0131ld\u0131z Technical University, Istanbul 34220, T\u00fcrkiye"}]},{"given":"Alir\u0131za","family":"\u0130slim","sequence":"additional","affiliation":[{"name":"Faculty of Art and Science, Molecular Biology and Genetics, Y\u0131ld\u0131z Technical University, Istanbul 34220, T\u00fcrkiye"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2917-8860","authenticated-orcid":false,"given":"Kevser K\u00fcbra","family":"K\u0131rbo\u011fa","sequence":"additional","affiliation":[{"name":"Bioengineering Department, Faculty of Engineering, Bilecik Seyh Edebali University, Bilecik 11100, T\u00fcrkiye"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8772-0542","authenticated-orcid":false,"given":"Derya","family":"Y\u0131ld\u0131z","sequence":"additional","affiliation":[{"name":"Faculty of Art and Science, Molecular Biology and Genetics, Y\u0131ld\u0131z Technical University, Istanbul 34220, T\u00fcrkiye"}]},{"given":"Nehir \u00d6zdemir","family":"\u00d6zgent\u00fcrk","sequence":"additional","affiliation":[{"name":"Faculty of Art and Science, Molecular Biology and Genetics, Y\u0131ld\u0131z Technical University, Istanbul 34220, T\u00fcrkiye"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8172-6633","authenticated-orcid":false,"given":"Mithun","family":"Rudrapal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Biotechnology and Pharmaceutical Sciences, Vignan\u2019s Foundation for Science, Technology and Research, Guntur 522213, India"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0044-4758","authenticated-orcid":false,"given":"Johra","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al Majmaah 11932, Saudi Arabia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8196-3703","authenticated-orcid":false,"given":"Raghu Ram","family":"Achar","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, School of Life Sciences, JSS Academy of Higher Education & Research, Mysuru 570015, India"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0246-5149","authenticated-orcid":false,"given":"Ekaterina","family":"Silina","sequence":"additional","affiliation":[{"name":"Institute of Digital Biodesign and Modeling of Living Systems, I. M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119991, Russia"}]},{"given":"Natalia","family":"Manturova","sequence":"additional","affiliation":[{"name":"Department of Surgery, Pirogov Russian National Research Medical University, Moscow 117997, Russia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9522-8061","authenticated-orcid":false,"given":"Victor","family":"Stupin","sequence":"additional","affiliation":[{"name":"Department of Surgery, Pirogov Russian National Research Medical University, Moscow 117997, Russia"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hatayama, M., and Aruga, J. (2023). Developmental control of noradrenergic system by SLITRK1 and its implications in the pathophysiology of neuropsychiatric disorders. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.1080739"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"De Luca, C., Colangelo, A.M., Virtuoso, A., Alberghina, L., and Papa, M. (2020). Neurons, Glia, Extracellular Matrix and Neurovascular Unit: A Systems Biology Approach to the Complexity of Synaptic Plasticity in Health and Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041539"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.jmb.2004.02.002","article-title":"Prediction and functional analysis of native disorder in proteins from the three kingdoms of life","volume":"337","author":"Ward","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3389\/fphy.2019.00010","article-title":"Intrinsically Disordered Proteins and Their \u201cMysterious\u201d (Meta)Physics","volume":"7","author":"Uversky","year":"2019","journal-title":"Front. Phys."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1126\/science.1228775","article-title":"Structural biology. Versatility from protein disorder","volume":"337","author":"Babu","year":"2012","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.tibs.2012.08.004","article-title":"Intrinsically disordered proteins: A 10-year recap","volume":"37","author":"Tompa","year":"2012","journal-title":"Trends Biochem. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"W239","DOI":"10.1093\/nar\/gkl190","article-title":"CUPSAT: Prediction of protein stability upon point mutations","volume":"34","author":"Parthiban","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.sbi.2009.08.003","article-title":"Stability effects of mutations and protein evolvability","volume":"19","author":"Tokuriki","year":"2009","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/nrm3920","article-title":"Intrinsically disordered proteins in cellular signalling and regulation","volume":"16","author":"Wright","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/nrn1517","article-title":"PDZ domain proteins of synapses","volume":"5","author":"Kim","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.tcb.2013.07.004","article-title":"LAR-RPTPs: Synaptic adhesion molecules that shape synapse development","volume":"23","author":"Um","year":"2013","journal-title":"Trends Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1021\/ac051437y","article-title":"XCMS:\u2009 Processing Mass Spectrometry Data for Metabolite Profiling Using Nonlinear Peak Alignment, Matching, and Identification","volume":"78","author":"Smith","year":"2006","journal-title":"Anal. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13384","DOI":"10.3390\/molecules200713384","article-title":"Molecular docking and structure-based drug design strategies","volume":"20","author":"Ferreira","year":"2015","journal-title":"Molecules"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00221-021-06229-y","article-title":"Non-invasive brain stimulation as therapy: Systematic review and recommendations with a focus on the treatment of Tourette syndrome","volume":"240","author":"Dyke","year":"2022","journal-title":"Exp. Brain Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1126\/science.1187409","article-title":"Atomic-Level Characterization of the Structural Dynamics of Proteins","volume":"330","author":"Shaw","year":"2010","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5113","DOI":"10.1021\/jp508971m","article-title":"Water Dispersion Interactions Strongly Influence Simulated Structural Properties of Disordered Protein States","volume":"119","author":"Piana","year":"2015","journal-title":"J. Phys. Chem. B"},{"key":"ref_17","first-page":"65","article-title":"Molecular docking: Current advances and challenges","volume":"21","author":"Arciniega","year":"2018","journal-title":"TIP Rev. Espec. En Cienc. Qu\u00edmico-Biol\u00f3gicas"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.str.2020.08.005","article-title":"A Global Ramachandran Score Identifies Protein Structures with Unlikely Stereochemistry","volume":"28","author":"Sobolev","year":"2020","journal-title":"Structure"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.sbi.2020.07.001","article-title":"Challenges in protein docking","volume":"64","author":"Vakser","year":"2020","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3390\/ddc3010009","article-title":"Revolutionizing Drug Discovery: A Comprehensive Review of AI Applications","volume":"3","author":"Dhudum","year":"2024","journal-title":"Drugs Drug Candidates"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1109\/TNN.1998.712192","article-title":"Reinforcement Learning: An Introduction","volume":"9","author":"Sutton","year":"2018","journal-title":"IEEE Trans. Neural Netw."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gj\u00e6rum, V.B., R\u00f8rvik, E.L.H., and Lekkas, A.M. (July, January 29). Approximating a deep reinforcement learning docking agent using linear model trees. Proceedings of the 2021 European Control Conference (ECC), Naples, Italy.","DOI":"10.23919\/ECC54610.2021.9655007"},{"key":"ref_23","unstructured":"Abadi, M., Barham, P., Chen, J., Chen, Z., Davis, A., Dean, J., Devin, M., Ghemawat, S., Irving, G., and Isard, M. (2016). TensorFlow: A System for Large-Scale Machine Learning. arXiv, Available online: https:\/\/arxiv.org\/abs\/1605.08695."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nrd3913","article-title":"Objective assessment of cancer genes for drug discovery","volume":"12","author":"Patel","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"W344","DOI":"10.1093\/nar\/gkw408","article-title":"ConSurf 2016: An improved methodology to estimate and visualize evolutionary conservation in macromolecules","volume":"44","author":"Ashkenazy","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Salo-Ahen, O.M.H., Alanko, I., Bhadane, R., Bonvin, A.M.J.J., Honorato, R.V., Hossain, S., Juffer, A.H., Kabedev, A., Lahtela-Kakkonen, M., and Larsen, A.S. (2021). Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development. Processes, 9.","DOI":"10.3390\/pr9010071"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Jeyasri, R., Muthuramalingam, P., Suba, V., Ramesh, M., and Chen, J.T. (2020). Bacopa monnieri and Their Bioactive Compounds Inferred Multi-Target Treatment Strategy for Neurological Diseases: A Cheminformatics and System Pharmacology Approach. Biomolecules, 10.","DOI":"10.3390\/biom10040536"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"D20","DOI":"10.1093\/nar\/gkab1112","article-title":"Database resources of the national center for biotechnology information","volume":"50","author":"Sayers","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.pediatrneurol.2012.08.015","article-title":"Metabolic Effects of Aripiprazole and Pimozide in Children With Tourette Syndrome","volume":"47","author":"Rizzo","year":"2012","journal-title":"Pediatr. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.neuropharm.2012.05.043","article-title":"Pharmacological treatment of tic disorders and Tourette Syndrome","volume":"68","author":"Roessner","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1212\/WNL.0000000000007467","article-title":"Comprehensive systematic review summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders","volume":"92","author":"Pringsheim","year":"2019","journal-title":"Neurology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1177\/02698811211032445","article-title":"Pharmacological treatment for Tourette syndrome in children and adults: What is the quality of the evidence? A systematic review","volume":"35","author":"Besag","year":"2021","journal-title":"J. Psychopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e1259708","DOI":"10.1080\/21690707.2016.1259708","article-title":"How disordered is my protein and what is its disorder for? A guide through the \u201cdark side\u201d of the protein universe","volume":"4","author":"Lieutaud","year":"2016","journal-title":"Intrinsically Disord. Proteins"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"W141","DOI":"10.1093\/nar\/gkad330","article-title":"DEPICTER2: A comprehensive webserver for intrinsic disorder and disorder function prediction","volume":"51","author":"Basu","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"W62","DOI":"10.1093\/nar\/gkad430","article-title":"CAID prediction portal: A comprehensive service for predicting intrinsic disorder and binding regions in proteins","volume":"51","author":"Bouhraoua","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.1007\/s00018-017-2555-4","article-title":"Comprehensive review of methods for prediction of intrinsic disorder and its molecular functions","volume":"74","author":"Meng","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"ELIXIR-1753","DOI":"10.12688\/f1000research.20136.1","article-title":"An intrinsically disordered proteins community for ELIXIR [version 1; peer review: 2 approved]","volume":"8","author":"Davey","year":"2019","journal-title":"F1000Research"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/cr.2009.87","article-title":"Predicting intrinsic disorder in proteins: An overview","volume":"19","author":"He","year":"2009","journal-title":"Cell Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1800415","DOI":"10.1002\/pmic.201800415","article-title":"On the Need to Develop Guidelines for Characterizing and Reporting Intrinsic Disorder in Proteins","volume":"19","author":"Vincent","year":"2019","journal-title":"Proteomics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"W306","DOI":"10.1093\/nar\/gki375","article-title":"I-Mutant2.0: Predicting stability changes upon mutation from the protein sequence or structure","volume":"33","author":"Capriotti","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/pro.4218","article-title":"PANTHER: Making genome-scale phylogenetics accessible to all","volume":"31","author":"Thomas","year":"2022","journal-title":"Protein Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"W247","DOI":"10.1093\/nar\/gkx369","article-title":"PhD-SNPg: A webserver and lightweight tool for scoring single nucleotide variants","volume":"45","author":"Capriotti","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"62219","DOI":"10.1007\/s11356-021-17799-3","article-title":"Paternal factors in recurrent pregnancy loss: An insight through analysis of non-synonymous single-nucleotide polymorphism in human testis-specific chaperone HSPA2 gene","volume":"29","author":"Mohanty","year":"2022","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein\u2013protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/pro.3978","article-title":"The BioGRID database: A comprehensive biomedical resource of curated protein, genetic, and chemical interactions","volume":"30","author":"Oughtred","year":"2021","journal-title":"Protein Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/s41467-023-44680-3","article-title":"Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development","volume":"15","author":"Shah","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1111\/j.1742-4658.2005.04691.x","article-title":"A novel transmembrane topology of presenilin based on reconciling experimental and computational evidence","volume":"272","author":"Henricson","year":"2005","journal-title":"FEBS J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"W429","DOI":"10.1093\/nar\/gkm256","article-title":"Advantages of combined transmembrane topology and signal peptide prediction\u2014The Phobius web server","volume":"35","author":"Krogh","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e4582","DOI":"10.1002\/pro.4582","article-title":"Using evolutionary data to make sense of macromolecules with a \u201cface-lifted\u201d ConSurf","volume":"32","author":"Yariv","year":"2023","journal-title":"Protein Sci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Walker, J.M. (2005). Protein Identification and Analysis Tools on the ExPASy Server. The Proteomics Protocols Handbook, Humana Press.","DOI":"10.1385\/1592598900"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.jgeb.2017.05.003","article-title":"An in silico structural, functional and phylogenetic analysis with three dimensional protein modeling of alkaline phosphatase enzyme of Pseudomonas aeruginosa","volume":"15","author":"Pramanik","year":"2017","journal-title":"J. Genet. Eng. Biotechnol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nprot.2015.053","article-title":"The Phyre2 web portal for protein modeling, prediction and analysis","volume":"10","author":"Kelley","year":"2015","journal-title":"Nat. Protoc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1073\/pnas.1914677117","article-title":"Improved protein structure prediction using predicted interresidue orientations","volume":"117","author":"Yang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1016\/j.bbamem.2017.09.016","article-title":"Molecular analysis of human solute carrier SLC26 anion transporter disease-causing mutations using 3-dimensional homology modeling","volume":"1859","author":"Rapp","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Biomembr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A Visualization System for Exploratory Research and Analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_56","unstructured":"Singh, D.B., and Pathak, R.K. (2022). Chapter 11\u2014Protein structure prediction. Bioinformatics, Academic Press."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/bs.apcsb.2022.10.010","article-title":"Chapter Ten\u2014Structure-based virtual screening to identify potential lipase inhibitors to reduce lipid storage in Wolman disorder","volume":"Volume 133","author":"Donev","year":"2023","journal-title":"Advances in Protein Chemistry and Structural Biology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1038\/s41596-020-0312-x","article-title":"The HDOCK server for integrated protein\u2013protein docking","volume":"15","author":"Yan","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.52711\/0974-360X.2023.00407","article-title":"In Silico Identification of Potential Inhibitors of Substituted Quinazolin-4-One against Main Protease and Spike Glycoprotein of Sars Cov-2","volume":"16","author":"K","year":"2023","journal-title":"Res. J. Pharm. Technol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s12551-016-0247-1","article-title":"Software for molecular docking: A review","volume":"9","author":"Pagadala","year":"2017","journal-title":"Biophys. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/nature14236","article-title":"Human-level control through deep reinforcement learning","volume":"518","author":"Mnih","year":"2015","journal-title":"Nature"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Wang, Z., Wang, S., Li, Y., Guo, J., Wei, Y., Mu, Y., Zheng, L., and Li, W. (2024). A new paradigm for applying deep learning to protein-ligand interaction prediction. Brief. Bioinform., 25.","DOI":"10.1093\/bib\/bbae145"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6800","DOI":"10.1039\/D0CP06378A","article-title":"Reinforcement learning to boost molecular docking upon protein conformational ensemble","volume":"23","author":"Chong","year":"2021","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"106948","DOI":"10.1016\/j.dib.2021.106948","article-title":"Dataset of AMBER force field parameters of drugs, natural products and steroids for simulations using GROMACS","volume":"35","author":"Loschwitz","year":"2021","journal-title":"Data Brief."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1021\/acs.jcim.2c00044","article-title":"GROMACS in the Cloud: A Global Supercomputer to Speed Up Alchemical Drug Design","volume":"62","author":"Kutzner","year":"2022","journal-title":"J. Chem. Inf. Model."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e30294","DOI":"10.7554\/eLife.30294","article-title":"Intrinsically disordered linkers determine the interplay between phase separation and gelation in multivalent proteins","volume":"6","author":"Harmon","year":"2017","journal-title":"eLife"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1146\/annurev-physchem-012420-104917","article-title":"Single-Molecule FRET of Intrinsically Disordered Proteins","volume":"71","author":"Metskas","year":"2020","journal-title":"Annu. Rev. Phys. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4412","DOI":"10.1080\/07391102.2023.2220814","article-title":"A comprehensive examination of ACE2 receptor and prediction of spike glycoprotein and ACE2 interaction based on in silico analysis of ACE2 receptor","volume":"42","year":"2024","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S1044-7431(03)00129-5","article-title":"Identification and characterization of Slitrk, a novel neuronal transmembrane protein family controlling neurite outgrowth","volume":"24","author":"Aruga","year":"2003","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1146\/annurev.biophys.33.110502.140348","article-title":"Disease-Related Misassembly of Membrane Proteins","volume":"33","author":"Sanders","year":"2004","journal-title":"Annu. Rev. Biophys."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Nugent, T., and Jones, D.T. (2009). Transmembrane protein topology prediction using support vector machines. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-159"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20080295","article-title":"Protein stability and aggregation in Parkinson\u2019s disease","volume":"413","author":"Robinson","year":"2008","journal-title":"Biochem. J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/nature10317","article-title":"Molecular chaperones in protein folding and proteostasis","volume":"475","author":"Hartl","year":"2011","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/ajmg.b.32608","article-title":"Association of IMMP2L deletions with autism spectrum disorder: A trio family study and meta-analysis","volume":"177","author":"Zhang","year":"2018","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"112057","DOI":"10.1016\/j.bbr.2019.112057","article-title":"First behavioural assessment of a novel Immp2l knockdown mouse model with relevance for Gilles de la Tourette syndrome and Autism spectrum disorder","volume":"374","author":"Kreilaus","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"556803","DOI":"10.3389\/fpsyt.2020.556803","article-title":"Tourette Syndrome Risk Genes Regulate Mitochondrial Dynamics, Structure, and Function","volume":"11","author":"Clarke","year":"2021","journal-title":"Front. Psychiatry"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/1348-0421.13098","article-title":"Bioinformatic investigation of Nipah virus surface protein mutations: Molecular docking with Ephrin B2 receptor, molecular dynamics simulation, and structural impact analysis","volume":"67","author":"Kahveci","year":"2023","journal-title":"Microbiol. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5686","DOI":"10.1080\/07391102.2023.2227720","article-title":"Role of death-associated protein kinase 1 (DAPK1) in retinal degenerative diseases: An in-silico approach towards therapeutic intervention","volume":"42","author":"Firoz","year":"2024","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Wang, C., Chen, Y., Zhang, Y., Li, K., Lin, M., Pan, F., Wu, W., and Zhang, J. (2022). A reinforcement learning approach for protein\u2013ligand binding pose prediction. BMC Bioinform., 23.","DOI":"10.1186\/s12859-022-04912-7"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Ramdane-Cherif, A., Singh, T.P., Tomar, R., Choudhury, T., and Um, J.-S. (2023). Applications of deep reinforcement learning for drug discovery. Machine Intelligence and Data Science Applications, Singapore, Springer.","DOI":"10.1007\/978-981-99-1620-7"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41392-024-02036-3","article-title":"New insights into protein\u2013protein interaction modulators in drug discovery and therapeutic advance","volume":"9","author":"Nada","year":"2024","journal-title":"Sig. Transduct. Target. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e2303165121","DOI":"10.1073\/pnas.2303165121","article-title":"Reinforcement learning informs optimal treatment strategies to limit antibiotic resistance","volume":"121","author":"Weaver","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Computation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-3197\/13\/2\/29\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:37:18Z","timestamp":1759919838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-3197\/13\/2\/29"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,27]]},"references-count":82,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["computation13020029"],"URL":"https:\/\/doi.org\/10.3390\/computation13020029","relation":{},"ISSN":["2079-3197"],"issn-type":[{"type":"electronic","value":"2079-3197"}],"subject":[],"published":{"date-parts":[[2025,1,27]]}}}