title: Toward in silico biomolecular manipulation through static modes: atomic scale characterization of HIV-1 protease flexibility.
abstract: Probing biomolecular flexibility with atomic-scale resolution is a challenging task in current computational biology for fundamental understanding and prediction of biomolecular interactions and associated functions. This paper makes use of the static mode method to study HIV-1 protease considered as a model system to investigate the full biomolecular flexibility at the atomic scale, the screening of active site biomechanical properties, the blind prediction of allosteric sites, and the design of multisite strategies to target deformations of interest. Relying on this single calculation run of static modes, we demonstrate that in silico predictive design of an infinite set of complex excitation fields is reachable, thanks to the storage of the static modes in a data bank that can be used to mimic single or multiatom contact and efficiently anticipate conformational changes arising from external stimuli. All along this article, we compare our results to data previously published and propose a guideline for efficient, predictive, and custom in silico experiments.
authors.affiliation: CNRS , LAAS, 7 avenue du colonel Roche, F-31400 Toulouse, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Brut
authors.forename: Alain
authors.initials: A
authors.lastname: Estève
authors.forename: Georges
authors.initials: G
authors.lastname: Landa
authors.forename: Mehdi
authors.initials: M
authors.lastname: Djafari Rouhani
mesh_terms: D020134:Catalytic Domain; D003198:Computer Simulation; D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D018625:Microscopy, Atomic Force; D008954:Models, Biological
chemical_list: D008024:Ligands; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1