The ff94 force field that is commonly associated with the Amber simulation package is one of the most widely used parameter sets for biomolecular simulation. After a decade of extensive use and testing, limitations in this force field, such as over-stabilization of alpha-helices, were reported by us and other researchers. This led to a number of attempts to improve these parameters, resulting in a variety of "Amber" force fields and significant difficulty in determining which should be used for a particular application. We show that several of these continue to suffer from inadequate balance between different secondary structure elements. In addition, the approach used in most of these studies neglected to account for the existence in Amber of two sets of backbone phi/psi dihedral terms. This led to parameter sets that provide unreasonable conformational preferences for glycine. We report here an effort to improve the phi/psi dihedral terms in the ff99 energy function. Dihedral term parameters are based on fitting the energies of multiple conformations of glycine and alanine tetrapeptides from high level ab initio quantum mechanical calculations. The new parameters for backbone dihedrals replace those in the existing ff99 force field. This parameter set, which we denote ff99SB, achieves a better balance of secondary structure elements as judged by improved distribution of backbone dihedrals for glycine and alanine with respect to PDB survey data. It also accomplishes improved agreement with published experimental data for conformational preferences of short alanine peptides and better accord with experimental NMR relaxation data of test protein systems.

/pdf/comparison-of-multiple-amber-force-fields-and-development-of-2mpeu0hj18.pdf

Comparison of multiple Amber force fields and development of improved protein backbone parameters.

BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

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Ru(II) polypyridine complexes: photophysics, photochemistry, eletrochemistry, and chemiluminescence

Protein structures in the Protein Data Bank provide a wealth of data about the interactions that determine the native states of proteins. Using the probability theory, we derive an atomic distance-dependent statistical potential from a sample of native structures that does not depend on any adjustable parameters (Discrete Optimized Protein Energy, or DOPE). DOPE is based on an improved reference state that corresponds to noninteracting atoms in a homogeneous sphere with the radius dependent on a sample native structure; it thus accounts for the finite and spherical shape of the native structures. The DOPE potential was extracted from a nonredundant set of 1472 crystallographic structures. We tested DOPE and five other scoring functions by the detection of the native state among six multiple target decoy sets, the correlation between the score and model error, and the identification of the most accurate non-native structure in the decoy set. For all decoy sets, DOPE is the best performing function in terms of all criteria, except for a tie in one criterion for one decoy set. To facilitate its use in various applications, such as model assessment, loop modeling, and fitting into cryo-electron microscopy mass density maps combined with comparative protein structure modeling, DOPE was incorporated into the modeling package MODELLER-8.

/pdf/statistical-potential-for-assessment-and-prediction-of-16jn1n7saa.pdf

Statistical potential for assessment and prediction of protein structures

In this paper we present a unified treatment of non-radiative decay processes in large molecules which involve either electronic relaxation between two electronic states or unimolecular rearrangeme...

The energy gap law for radiationless transitions in large molecules

Polyatomic molecules radiationless transition rate statistical analysis, suggesting role of Franck-Condon principle in determination of nonradiative decay rates

Multiphonon Processes in the Nonradiative Decay of Large Molecules

Brief Summary of the Configurational Statistics of Polymer Chains Introduction to Functional Integration: Flexible Polymer Chains The Excluded Volume Problem: Introduction Scaling Theory Renormalization Group Description of Polymer Excluded Volume Use of Perturbation and E-expansions in Renormalization Group Treatment of Polymers Crossover Dependence Concentration Dependence Comparison with Experiment The Theta-point Region Connections with Field Theory Methods Evaluation of Scaling Functions of Variables Other than U Appendixes Index.

Renormalization Group Theory of Macromolecules

An unfolded state ensemble is generated by using a self-avoiding statistical coil model that is based on backbone conformational frequencies in a coil library, a subset of the Protein Data Bank. The model reproduces two apparently contradicting behaviors observed in the chemically denatured state for a variety of proteins, random coil scaling of the radius of gyration and the presence of significant amounts of local backbone structure (NMR residual dipolar couplings). The most stretched members of our unfolded ensemble dominate the residual dipolar coupling signal, whereas the uniformity of the sign of the couplings follows from the preponderance of polyproline II and β conformers in the coil library. Agreement with the NMR data substantially improves when the backbone conformational preferences include correlations arising from the chemical and conformational identity of neighboring residues. Although the unfolded ensembles match the experimental observables, they do not display evidence of native-like topology. By providing an accurate representation of the unfolded state, our statistical coil model can be used to improve thermodynamic and kinetic modeling of protein folding.

http://www.cs.duke.edu/brd/Teaching/Bio/asmb/current/Papers/13099.pdf

Statistical coil model of the unfolded state: Resolving the reconciliation problem

Experimental and Monte Carlo data for the dilute-solution properties of «lightly branched» polymers (stars, combs, rings, ...) are compared with the renormalization group predictions of Douglas and Freed. The comparisons focus on «universal] dimensionless ratios of the mean dimensions of lightly branched polymers, relative to those of linear polymers having the same molecular weight. Dimensionless ratios involving the polymer second virial coefficient, A 2 , are also tabulated and compared with theory

Characterization of branching architecture through "universal" ratios of polymer solution properties

Effect of monomer structure and compressibility on the properties of multicomponent polymer blends and solutions: 1. Lattice cluster theory of compressible systems

Karl F. Freed

Papers

Multiphonon Processes in the Nonradiative Decay of Large Molecules

Renormalization Group Theory of Macromolecules

Statistical coil model of the unfolded state: Resolving the reconciliation problem

Characterization of branching architecture through "universal" ratios of polymer solution properties

Effect of monomer structure and compressibility on the properties of multicomponent polymer blends and solutions: 1. Lattice cluster theory of compressible systems