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Martin Karplus

Publications and source records attributed to Martin Karplus.

79 records · Page 5Linked to original sources
PubMed2002

A dynamic analysis of the rotation mechanism for conformational change in F(1)-ATPase.

Molecular dynamics trajectories for the bovine mitochondrial F(1)-ATPase are used to demonstrate the motions and interactions that take place during the elementary (120 degrees rotation) step of the gamma subunit. The results show how rotation of the gamma subunit induces the observed structural changes in the catalytic beta subunits. Both steric and electrostatic interactions contribute. An "ionic track" of Arg and Lys residues on the protruding portion of the gamma subunit plays a role in guiding the motions of the beta subunits. Experimental data for mutants of the DELSEED motif and the hinge region are interpreted on the basis of the molecular dynamics results. The trajectory provides a unified dynamic description of the coupled subunit motions involved in the 120 degrees rotation cycles of F(1)-ATPase.

Crystallography, X-Ray↗
PubMed2002

Translocation mechanism of long sugar chains across the maltoporin membrane channel.

Maltoporin allows permeation of long maltodextrin chains. It tightly binds the amphiphilic sugar, offering both hydrophobic interactions with a helical lane of aromatic residues and H bonds with ionic side chains. The minimum-energy path of maltohexaose translocation is obtained by the conjugate peak refinement method, which optimizes a continuous string of conformers without applying constraints. This reveals that the protein is passive while the sugar glides screw-like along the aromatic lane. Near instant switching of sugar hydroxyl H bond partners results in two small energy barriers (of approximately 4 kcal/mol each) during register shift by one glucosyl unit, in agreement with a kinetic analysis of experimental dissociation rates for varying sugar chain lengths. Thus, maltoporin functions like an efficient translocation "enzyme," and the slow rate of the register shift (approximately 1/ms) is due to high collisional friction.

Bacterial Outer Membrane Proteins↗
PubMed2002

Free energy simulations come of age: protein-ligand recognition.

In recent years, molecular dynamics simulations of biomolecular free energy differences have benefited from significant methodological advances and increased computer power. Applications to molecular recognition provide an understanding of the interactions involved that goes beyond, and is an important complement to, experimental studies. Poisson-Boltzmann electrostatic models provide a faster and simpler free energy method in cases where electrostatic interactions are important. We illustrate both molecular dynamics and Poisson-Boltzmann methods with a detailed study of amino acid recognition by aspartyl-tRNA synthetase, whose specificity is important for maintaining the integrity of the genetic code.

Computer Simulation↗
PubMed2002

Molecular dynamics simulations of biomolecules.

Molecular dynamics simulations are important tools for understanding the physical basis of the structure and function of biological macromolecules. The early view of proteins as relatively rigid structures has been replaced by a dynamic model in which the internal motions and resulting conformational changes play an essential role in their function. This review presents a brief description of the origin and early uses of biomolecular simulations. It then outlines some recent studies that illustrate the utility of such simulations and closes with a discussion of their ever-increasing potential for contributing to biology.

Models, Molecular↗
PubMed2001

Comment on the Communication "The Key to Solving the Protein-Folding Problem Lies in an Accurate Description of the Denatured State" by van Gunsteren et al. We thank Eugene Shakhnovich (Harvard University) for pointing out the references on lattice polymer simulations and very helpful discussions. We also thank Wilfred van Gunsteren for comments on the manuscript. A.R.D. is a Burroughs Wellcome Fund Hitchings-Elion Postdoctoral Fellow. The work done at Harvard was supported in part by the National Institutes of Health.

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Journal Article↗
PubMed2001

Effective atom volumes for implicit solvent models: comparison between Voronoi volumes and minimum fluctuation volumes.

An essential element of implicit solvent models, such as the generalized Born method, is a knowledge of the volume associated with the individual atoms of the solute. Two approaches for determining atomic volumes for the generalized Born model are described; one is based on Voronoi polyhedra and the other, on minimizing the fluctuations in the overall volume of the solute. Volumes to be used with various parameter sets for protein and nucleic acids in the CHARMM force field are determined from a large set of known structures. The volumes resulting from the two different approaches are compared with respect to various parameters, including the size and solvent accessibility of the structures from which they are determined. The question of whether to include hydrogens in the atomic representation of the solute volume is examined. Copyright 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1857-1879, 2001

Journal Article↗