title: AlaScan: A Graphical User Interface for Alanine Scanning Free-Energy Calculations.
abstract: Computation of the free-energy changes that underlie molecular recognition and association has gained significant importance due to its considerable potential in drug discovery. The massive increase of computational power in recent years substantiates the application of more accurate theoretical methods for the calculation of binding free energies. The impact of such advances is the application of parent approaches, like computational alanine scanning, to investigate in silico the effect of amino-acid replacement in protein-ligand and protein-protein complexes, or probe the thermostability of individual proteins. Because human effort represents a significant cost that precludes the routine use of this form of free-energy calculations, minimizing manual intervention constitutes a stringent prerequisite for any such systematic computation. With this objective in mind, we propose a new plug-in, referred to as AlaScan, developed within the popular visualization program VMD to automate the major steps in alanine-scanning calculations, employing free-energy perturbation as implemented in the widely used molecular dynamics code NAMD. The AlaScan plug-in can be utilized upstream, to prepare input files for selected alanine mutations. It can also be utilized downstream to perform the analysis of different alanine-scanning calculations and to report the free-energy estimates in a user-friendly graphical user interface, allowing favorable mutations to be identified at a glance. The plug-in also assists the end-user in assessing the reliability of the calculation through rapid visual inspection.
authors.affiliation: Laboratoire International Associé Centre National de la Recherche Scientifique et University of Illinois at Urbana-Champaign, Unité Mixte de Recherche n°7565, Université de Lorraine , B.P. 70239, 54506 Vandœuvre-lès-Nancy cedex, France.
authors.forename: Vijayaraj
authors.initials: V
authors.lastname: Ramadoss
authors.affiliation: Laboratoire International Associé Centre National de la Recherche Scientifique et University of Illinois at Urbana-Champaign, Unité Mixte de Recherche n°7565, Université de Lorraine , B.P. 70239, 54506 Vandœuvre-lès-Nancy cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Dehez
authors.affiliation: Laboratoire International Associé Centre National de la Recherche Scientifique et University of Illinois at Urbana-Champaign, Unité Mixte de Recherche n°7565, Université de Lorraine , B.P. 70239, 54506 Vandœuvre-lès-Nancy cedex, France.|Department of Physics, University of Illinois at Urbana-Champaign , 1110 West Green Street, Urbana, Illinois 61801, United States.
authors.forename: Christophe
authors.initials: C
authors.lastname: Chipot
mesh_terms: D000409:Alanine; D019295:Computational Biology / Q000379:methods*; D003196:Computer Graphics; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics; D014584:User-Computer Interface
chemical_list: D011506:Proteins; D000409:Alanine