Improvements to REDCRAFT: a software tool for simultaneous characterization of protein backbone structure and dynamics from residual dipolar couplings.

Within the past two decades, there has been an increase in the acquisition of residual dipolar couplings (RDC) for investigations of biomolecular structures. Their use however is still not as widely adopted as the traditional methods of structure determination by NMR, despite their potential for extending the limits in studies that examine both the structure and dynamics of biomolecules. This is in part due to the difficulties associated with the analysis of this information-rich data type.

Dynafold: a dynamic programming approach to protein backbone structure determination from minimal sets of Residual Dipolar Couplings.

Residual Dipolar Couplings (RDCs) are a source of NMR data that can provide a powerful set of constraints on the orientation of inter-nuclear vectors, and are quickly becoming a larger part of the experimental toolset for molecular biologists. However, few reliable protocols exist for the determination of protein backbone structures from small sets of RDCs. DynaFold is a new dynamic programming algorithm designed specifically for this task, using minimal sets of RDCs collected in multiple alignment media.

Advances in the REDCAT software package.

Background: Residual Dipolar Couplings (RDCs) have emerged in the past two decades as an informative source of experimental restraints for the study of structure and dynamics of biological macromolecules and complexes. The REDCAT software package was previously introduced for the analysis of molecular structures using RDC data. Here we report additional features that have been included in this software package in order to expand the scope of its analyses.

An artificial neural network approach to improving the correlation between protein energetics and the backbone structure.

Computational approaches to modeling protein structures have made significant advances over the past decade. However, the current limitation in modeling protein structures is to produce protein structures consistently below the limit of 6 Å compared to their native structure. Therefore, improvement of protein structures consistently below the 6 Å limit using simulation of biophysical forces is of significant interest.

PolyAna: analyzing synonymous and nonsynonymous polymorphic sites.

PolyAna (available at http://www.biol.sc.

Conflicting selection pressures on T-cell epitopes in HIV-1 subtype B.

Analysis of population-level polymorphism in eight coding genes of human immunodeficiency virus type 1 (HIV-1) subtype B revealed evidence not only of past purifying selection, but also of abundant slightly deleterious nonsynonymous variants subject to ongoing purifying selection. Both CD4 and CTL epitopes showed an excess of nonsynonymous variants that were singletons (occurring in just one sequence) in our dataset. Overall, median gene diversities at polymorphic nonsynonymous sites were highest at sites located in neither CD4 nor CTL epitopes, while polymorphic nonsynonymous sites in CD4 epitopes revealed the lowest median gene diversity.

Conflicting selection pressures target the NS3 protein in hepatitis C virus genotypes 1a and 1b.

Analysis of complete polyprotein-encoding sequences of the two most prevalent genotypes of hepatitis C virus (HCV-1a and HCV-1b) revealed evidence of abundant, slightly deleterious nonsynonymous variants subject to ongoing purifying selection. In the case of both HCV-1a and HCV-1b, the NS3 protein demonstrated a high incidence of forward-and-backward or parallel nonsynonymous changes in CTL epitopes as measured by the phylogenetic consistency index. These results imply that certain nonsynonymous mutations have occurred frequently throughout the HCV-1a and HCV-1b phylogenies in the codons encoding the epitopes in NS3.

The evolutionary biology of poxviruses.

The poxviruses (family Poxviridae) are a family of double-stranded viruses including several species that infect humans and their domestic animals, most notably Variola virus (VARV), the causative agent of smallpox. The evolutionary biology of these viruses poses numerous questions, for which we have only partial answers at present. Here we review evidence regarding the origin of poxviruses, the frequency of host transfer in poxvirus history, horizontal transfer of host genes to poxviruses, and the population processes accounting for patterns of nucleotide sequence polymorphism.

Distinctive pattern of sequence polymorphism in the NS3 protein of hepatitis C virus type 1b reflects conflicting evolutionary pressures.

Analysis of complete polyprotein-encoding sequences of hepatitis C virus genotype 1b (HCV-1b) showed evidence not only of past purifying selection but also of abundant slightly deleterious non-synonymous variants subject to ongoing purifying selection. The NS3 protein (with protease and NTPase/helicase activity) revealed less evidence of purifying selection acting on the cytotoxic T cells (CTL) epitopes than did the other proteins, whereas outside the CTL epitopes NS3 was more conserved than the other proteins. Moreover, NS3 showed a high incidence of forward-and-backward or parallel non-synonymous changes in CTL epitopes, as measured by the consistency index across the phylogeny of HCV-1b genomes computed at non-singleton non-synonymous polymorphic sites.

Prediction of lipid-interacting amino acid residues from sequence features.

Proteins and lipids are integral components of cell membranes, and play important roles in cell signalling. Alterations of normal protein-lipid recognition may cause various diseases. However, molecular mechanisms underlying protein-lipid recognition are still poorly understood.