The generalized Born (GB) approximation is introduced in the context of the implicit solvent framework. The physical foundations of the model and its derivation from the underlying Poisson-Boltzmann model are presented in detail. Examples of various flavors of the basic GB model are discussed, followed by examples of recent applications of the approximation in molecular modeling and simulations...

Accurate and reliable pKa prediction is of significant interest, because it provides direct information of the protonation state of a protein and can be compared to experimental data. In this work pKa shifts of three aminoacids in proteins have been calculated using molecular dynamics free energy simulations with an explicit solvent and implicit Generalized Born solvent model. The direction of ...

MDM2 is a key regulator of the p53 tumor-suppressor protein. Here we study the effect of modifications of a p53 N-terminal fragment on its binding to MDM2, using implicit-solvent MD and MM-GB/SA calculations. We provide interpretation of existing experimental data and predict the effect of mutations on binding. Notably 1) We analyze the effect of regulatory phosphorylations at Ser/Thr residues ...

Temperature-based replica-exchange molecular dynamics (REMD), in which multiple simultaneous simulations, or replicas, are run at a range of temperatures, has become increasingly popular for exploring the energy landscape of biomolecular systems. The practical application of REMD toward systems of biomedical interest is often limited by the rapidly increasing number of replicas needed to model ...

Block copolymer nano-micelles are especially important in cancer treatment because of their fine dimensions. In this article, three systems of amphiphilic copolymers with similar lengths and different ratios of the hydrophobic and hydrophilic chains are studied using implicit-solvent coarse-grained molecular dynamics simulations. The factor fphil is defined as the ratio of the number...

The treatment of hydration effects in protein dynamics simulations varies in model complexity and spans the range from the computationally intensive microscopic evaluation to simple dielectric screening of charge-charge interactions. This paper compares different solvent models applied to the problem of estimating the free-energy differencebetween two loop conformations in acetylcholinesterase....

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X-ray crystallography and cryo-electron microscopy are two popular methods for the structure determination of biological molecules. Atomic structures are derived through the fitting and refinement of an initial model into electron density maps constructed by both experiments. Two computational approaches, MDFF and xMDFF, have been developed to facilitate this process by integrating the experime...

A numerical method using implicit surface representations is proposed to solve the linearized Poisson-Boltzmann equations that arise in mathematical models for the electrostatics of molecules in solvent. The proposed method used an implicit boundary integral formulation to derived a linear system defined on Cartesian nodes in a narrowband surrounding the closed surface that separate the molecul...