Molecular dynamics (MD) simulations of the activation domain of porcine procarboxypeptidase B (ADBp) were performed to examine the effect of using the particle-particle particle-mesh (P3M) or the reaction field (RF) method for calculating electrostatic interactions in simulations of highly charged proteins. Several structural, thermodynamic, and dynamic observables were derived from the MD traj...

Protein solubility and conformational stability are a result of a balance of interactions both within a protein and between protein and solvent. The electrostatic solvation free energy of oligoglycines, models for the peptide backbone, becomes more favorable with an increasing length, yet longer peptides collapse due to the formation of favorable intrapeptide interactions between CO dipoles, in...

Estimating protein-protein interaction energies is a very challenging task for current simulation protocols. Here, absolute binding free energies are reported for the complex H-Ras/C-Raf1 using the MM-PB(GB)SA approach, testing the internal consistency and model dependence of the results. Averaging gas-phase energies (MM), solvation free energies as determined by Generalized Born models (GB/SA)...

A new theory of solutions, the method of energy representation, is introduced by adopting the solute-solvent interaction energy as the coordinate of distribution functions. The density-functional theory is formulated over the energy coordinate, and an approximate functional for the solvation free energy is given in terms of energy distribution functions in the solution and reference solvent sys...

We present PAFMPB, an updated and parallel version of the AFMPB software package for fast calculation of molecular solvation-free energy. The new version has the following new features: (1) The adaptive fast multipole method and the boundary element methods are parallelized; (2) A tool is embedded for automatic molecular VDW/SAS surface mesh generation, leaving the requirement for a mesh file a...

The free energy of solvation, DeltaGS0, in octanol of organic compounds is quantitatively predicted from the molecular structure. The model, involving only three molecular descriptors, is obtained by multiple linear regression analysis from a data set of 147 compounds containing diverse organic functions, namely, halogenated and non-halogenated alkanes, alkenes, alkynes, aromatics, alcohols, al...

A new method of analysis of the factor contributing to solvation of small molecules is described. Approximations of the energetic contributions to the entry of a molecule into water have been derived from partition coefficient data of solutes and selected derivatives from a multiplicity of solvents. These include taking separate account energy of the cost of introduction of a molecular cavity i...

This tutorial explains how NAMD and related tools can be used to setup and perform alchemical freeenergy simulations, within the free-energy perturbation (FEP) and thermodynamic integration (TI) theories. The “zero-sum” transformation of ethane into ethane is used as an introductory example. FEP is then used to compute the free energy of charging a naked Lennard-Jones particle into a sodium ion...

Implicit solvent models are increasingly popular for estimating aqueous solvation (hydration) free energies in molecular simulations and other applications. In many cases, parameters for these models are derived to reproduce experimental values for small molecule hydration free energies. Often, these hydration free energies are computed for a single solute conformation, neglecting solute confor...

We have carried out free energy perturbation calculations on DNA double-stranded hexanucleotides. The sequence d(CGCGCG)2 has been "mutated" into d(CGTGCG).d(CGCACG) with the oligonucleotide in the A, B, and Z structural forms, both in vacuo and in aqueous solution. In addition, model free energy calculations have been carried out in which the electrostatic charges of the H-bonding groups of th...