Solvation thermodynamic mapping of molecular surfaces in AmberTools: GIST

Abstract

The expulsion of water from surfaces upon molecular recognition and non-specific association makes a major contribution to the free energy changes of these processes. In order to facilitate the characterization of water structure and thermodynamics on surfaces, we have incorporated Grid Inhomogeneous Solvation Theory (GIST) into the CPPTRAJ toolset of AmberTools. GIST is a grid-based implementation of Inhomogeneous fluid Solvation Theory, which analyzes the output from molecular dynamics simulations to map out solvation thermodynamic and structural properties on a high-resolution, three-dimensional grid. The CPPTRAJ implementation, called GIST-cpptraj, has a simple, easy-to-use command line interface, and is open source and freely distributed. We have also developed a set of open-source tools, called GISTPP, which facilitate the analysis of GIST output grids. Tutorials for both GIST-cpptraj and GISTPP can be found at ambermd.org.

Disassembling solvation free energies into local contributions—Toward a microscopic understanding of solvation processes

“…2 While the examples presented in this article are restricted to small molecular solutes for clarity, each technique has been employed to larger biomolecular systems including proteins [52][53][54][55] or have even been implemented into standard simulation packages. 56 This allows for direct applications to simulations of relevant drug targets to improve rational drug-design strategies, the characterization of biomolecular surfaces, or analysis of the heterogeneity of hydration water properties.…”

Structure‐Guided Synthesis and Evaluation of Small‐Molecule Inhibitors Targeting Protein–Protein Interactions of BRCA1 tBRCT Domain

“…The thermodynamic property files produced were then used to calculate thermodynamic properties of water molecules at each density cluster. The detailed procedure for calculating enthalpy and entropy can be found in AMBER Advanced tutorial 25, written by Ramsey et al . Using GistPP voxel with both high solvent density (>12) and energy (<‐1) were identified and grouped into clusters.…”

“…[22] With 0.5 of grid spacing 44, 50 and 44 grid increments were used along each coordinate axis, respectively.A sm entioned in Amber16 documentation bulk water density of 0.0329 molecules À3 was specified for the calculation. Output files g_O and g_H corresponds to density of oxygen and hydrogens centers found in each voxel were expressed in the units of the bulk density.T he thermodynamic property files produced were then used to calculate thermodynamic properties of water molecules at each density cluster.T he detailed procedure for calculating enthalpy and entropy can be found in AMBER Advanced tutorial 25, written by Ramsey et al [28] Using GistPP voxel with both high solvent density (> 12) and energy (<-1) were identified and grouped into clusters. Thermodynamic properties for each cluster were calculated by GistPP and reported as sum of all the voxel in each cluster.…”

Structural features underlying the activity of benzimidazole derivatives that target phosphopeptide recognition by the tandem BRCT domain of the BRCA1 protein

“…Thermodynamics of water in ligand binding site was analyzed by Grid based Inhomogeneous Solvation Theory (GIST) developed by Nguyen and co-workers [18]. Change in the free energy at the hydration site ΔGSolv can be estimated by Equation (i) [26].…”

“…To calculate ΔGSolv at each grid points in defined area a molecular simulation was carried out in explicit water model using Amber15 MD simulation package [26,27] including Cα atom with a force constant of 100 kcal/mol/Å.…”