{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:36:41Z","timestamp":1762929401492,"version":"3.45.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Comput. Neurosci."],"abstract":"<jats:p>\n                    Six variants associated with autism spectrum disorder (ASD) abnormally activate the WASP-family Verprolin-homologous protein (WAVE) regulatory complex (WRC), a critical regulator of actin dynamics. This abnormal activation may contribute to the pathogenesis of this disorder. Using molecular dynamics (MD) simulations, we recently investigated the structural dynamics of wild-type (WT) WRC and R87C, A455P, and Q725R WRC disease-linked variants. Here, by extending MD simulations to I664M, E665K, and D724H WRC, we suggest that\n                    <jats:italic>all<\/jats:italic>\n                    of the mutations weaken the interactions and affect intra-complex allosteric communication between the WAVE1 active C-terminal region (ACR) and the rest of the complex. This might contribute to an abnormal complex activation, a hallmark of WRC-linked ASD. In addition, all mutants but I664M destabilize the ACR V-helix and increase the participation of ACR in large-scale movements. All these features may also abnormally influence the inactive WRC toward a dysfunctional state. We hypothesize that small-molecule ligands counteracting these effects may help restore normal WRC regulation in ASD-related variants.\n                  <\/jats:p>","DOI":"10.3389\/fncom.2025.1704350","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:32:33Z","timestamp":1762929153000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Common characteristics of variants linked to autism spectrum disorder in the WAVE regulatory complex"],"prefix":"10.3389","volume":"19","author":[{"given":"Song","family":"Xie","sequence":"first","affiliation":[]},{"given":"Ke","family":"Zuo","sequence":"additional","affiliation":[]},{"given":"Silvia","family":"De Rubeis","sequence":"additional","affiliation":[]},{"given":"Giorgio","family":"Bonollo","sequence":"additional","affiliation":[]},{"given":"Giorgio","family":"Colombo","sequence":"additional","affiliation":[]},{"given":"Paolo","family":"Ruggerone","sequence":"additional","affiliation":[]},{"given":"Paolo","family":"Carloni","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.cplett.2003.12.039","article-title":"Molecular dynamics simulations of water and biomolecules with a Monte Carlo constant pressure algorithm","volume":"384","author":"\u00c5qvist","year":"2004","journal-title":"Chem. 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