computer modeling in molecular biology.pdf

Computer Modelling in Molecular BiologyEdited by Julia M . GoodfellowOVCH Verlagsgesellschaft mbH. 19954 Molecular Dynamics andFree Energy Calculations Appliedto the Enzyme Barnase andOne of its Stability MutantsShoshana J Wodak. Daniel van Belle. and Martine Prt!vostUniversitC Libre de Bruxelles. Unit6 de Conformation de MacromolCculesBiologiques. CP160/16. P2. Ave . P . HCger. B-1050 Bruxelles. BelgiumContents4.1 Introduction ...................................................... 624.24.2.14.2.1.14.2.1.24.2.1.34.2.1.44.2.24.2.2.14.2.2.24.2.2.34.2.34.2.3.14.2.3.24.34.3.14.3.24.3.2.14.3.2.24.3.34.3.44.3.5Molecular Dynamics Simulations of Barnase in Water .................. 63Simulation Methodology ........................................... 64Integration Algorithm .............................................. 64The Force-Field ................................................... 65Treatment of Long-Range Coulombic Interactions ..................... 67Starting Conformation and Simulation Conditions ..................... 68Analysis of the 250 ps Trajectory of Barnase in Water ................. 71Protein Motion .................................................... 71Variations of the Protein Accessible Surface Area and Volume .......... 73Hydrogen Bonds .................................................. 74Structural and Dynamic Properties of Water Molecules Near theProtein Surface .................................................... 80Structural Properties ............................................... 80Dynamic Properties ................................................ 82Computing the Free Energy Change Associated with a HydrophobicMutation in Barnase ............................................... 86The Free Energy Perturbation Method ............................... 86Computing Free Energy Differences : Practical Aspects ................. 88Implementation of the Perturbation Method .......................... 88The Molecular Systems and Simulation Procedure ..................... 89Computed Changes in Protein Stability for the Ile 96 + Ala Mutation .... 91Error Estimation .................................................. 94Protein Stability and the Hydrophobic Effect ......................... 954.4 Concluding Remarks ............................................... 98References ........................................................ 99