{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T12:28:51Z","timestamp":1773664131020,"version":"3.50.1"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Electrostatic interactions play a crucial role in many biomolecular processes, including molecular recognition and binding. Biomolecular electrostatics is modulated to a large extent by the water surrounding the molecules. Here, we present a novel approach to the computation of electrostatic potentials which allows the inclusion of water structure into the classical theory of continuum electrostatics. Based on our recent purely differential formulation of nonlocal electrostatics [Hildebrandt, et al. (2004)Phys. Rev. Lett., 93, 108104] we have developed a new algorithm for its efficient numerical solution. The key component of this algorithm is a boundary element solver, having the same computational complexity as established boundary element methods for local continuum electrostatics. This allows, for the first time, the computation of electrostatic potentials and interactions of large biomolecular systems immersed in water including effects of the solvent's structure in a continuum description. We illustrate the applicability of our approach with two examples, the enzymes trypsin and acetylcholinesterase. The approach is applicable to all problems requiring precise prediction of electrostatic interactions in water, such as protein\u2013ligand and protein\u2013protein docking, folding and chromatin regulation. Initial results indicate that this approach may shed new light on biomolecular electrostatics and on aspects of molecular recognition that classical local electrostatics cannot reveal.<\/jats:p><jats:p>Contact: \u00a0anhi@bioinf.uni-sb.de<\/jats:p>","DOI":"10.1093\/bioinformatics\/btl312","type":"journal-article","created":{"date-parts":[[2007,1,19]],"date-time":"2007-01-19T18:51:12Z","timestamp":1169232672000},"page":"e99-e103","source":"Crossref","is-referenced-by-count":37,"title":["Electrostatic potentials of proteins in water: a structured continuum approach"],"prefix":"10.1093","volume":"23","author":[{"given":"Andreas","family":"Hildebrandt","sequence":"first","affiliation":[{"name":"Center for Bioinformatics, Saarland University 1 \u00a0 1 \u00a0 \u00a0 PO 15 11 50, 66041 Saarbr\u00fccken, Germany"}]},{"given":"Ralf","family":"Blossey","sequence":"additional","affiliation":[{"name":"Interdisciplinary Research Institute c\/o IEMN, Cit\u00e9 Scientifique BP 69 2 \u00a0 2 \u00a0 \u00a0 F-59652 Villeneuve d'Ascq, France"}]},{"given":"Sergej","family":"Rjasanow","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Saarland University 3 \u00a0 3 \u00a0 \u00a0 PO 15 11 50, 66041 Saarbr\u00fccken, Germany"}]},{"given":"Oliver","family":"Kohlbacher","sequence":"additional","affiliation":[{"name":"Department for Simulation of Biological Systems, WSI\/ZBIT, University of T\u00fcbingen, Sand 14 4 \u00a0 4 \u00a0 \u00a0 72070 T\u00fcbingen, Germany"}]},{"given":"Hans-Peter","family":"Lenhof","sequence":"additional","affiliation":[{"name":"Center for Bioinformatics, Saarland University 1 \u00a0 1 \u00a0 \u00a0 PO 15 11 50, 66041 Saarbr\u00fccken, Germany"}]}],"member":"286","published-online":{"date-parts":[[2007,1,15]]},"reference":[{"key":"2023041107151838600_","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/(SICI)1097-0282(199607)39:1<85::AID-BIP9>3.0.CO;2-R","article-title":"Acetylcholinesterase: role of the enzyme's charge distribution in steering charged ligands toward the active site","volume":"39","author":"Antosiewicz","year":"1996","journal-title":"Biopolymers"},{"key":"2023041107151838600_","doi-asserted-by":"crossref","first-page":"10037","DOI":"10.1073\/pnas.181342398","article-title":"Electrostatics of nanosystems: application to microtubules and the ribosome","volume":"98","author":"Baker","year":"2001","journal-title":"Proc. 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Chem."},{"key":"2023041107151838600_","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1021\/bi00053a003","article-title":"Acetylcholinesterase: electrostatic steering increases the rate of ligand binding","volume":"32","author":"Tan","year":"1993","journal-title":"Biochemistry"},{"key":"2023041107151838600_","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/1097-0282(2001)60:2<124::AID-BIP1008>3.0.CO;2-S","article-title":"Rapid boundary element solvation electrostatics calculations in folding simulations: successful folding of a 23\u2013residue peptide","volume":"60","author":"Totrov","year":"2001","journal-title":"Biopolymers"},{"key":"2023041107151838600_","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0167-8191(00)00087-9","article-title":"Automated empirical optimization of software and the ATLAS project","volume":"27","author":"Whaley","year":"2001","journal-title":"Parallel Comput."},{"key":"2023041107151838600_","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/BF00124405","article-title":"Smart: a solvent-accessible triangulated surface generator for molecular graphics and boundary element applications","volume":"9","author":"Zauhar","year":"1995","journal-title":"J. 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