Alexander D. MacKerell

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Computational studies of proteins based on empirical force fields represent a powerful tool to obtain structure-function relationships at an atomic level, and are central in current efforts to solve the protein folding problem. The results from studies applying these tools are, however, dependent on the quality of the force fields used. In particular,(More)
CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecular simulation program. It has been developed over the last three decades with a primary focus on molecules of biological interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals,(More)
The widely used CHARMM additive all-atom force field includes parameters for proteins, nucleic acids, lipids, and carbohydrates. In the present article, an extension of the CHARMM force field to drug-like molecules is presented. The resulting CHARMM General Force Field (CGenFF) covers a wide range of chemical groups present in biomolecules and drug-like(More)
Molecular mechanics force fields are widely used in computer-aided drug design for the study of drug-like molecules alone or interacting with biological systems. In simulations involving biological macromolecules, the biological part is typically represented by a specialized biomolecular force field, while the drug is represented by a matching general(More)
Presented is an extension of the CHARMM General Force Field (CGenFF) to enable the modeling of sulfonyl-containing compounds. Model compounds containing chemical moieties such as sulfone, sulfonamide, sulfonate, and sulfamate were used as the basis for the parameter optimization. Targeting high-level quantum mechanical and experimental crystal data, the new(More)
Molecular mechanics force fields are widely used in computer-aided drug design for the study of drug candidates interacting with biological systems. In these simulations, the biological part is typically represented by a specialized biomolecular force field, while the drug is represented by a matching general (organic) force field. In order to apply these(More)
A fluctuating charge (FQ) force field is applied to molecular dynamics simulations for six small proteins in explicit polarizable solvent represented by the TIP4P-FQ potential. The proteins include 1FSV, 1ENH, 1PGB, 1VII, 1H8K, and 1CRN, representing both helical and beta-sheet secondary structural elements. Constant pressure and temperature (NPT) molecular(More)
Empirical force field-based studies of biological macromolecules are becoming a common tool for investigating their structure-activity relationships at an atomic level of detail. Such studies facilitate interpretation of experimental data and allow for information not readily accessible to experimental methods to be obtained. A large part of the success of(More)