VIPERdb (http://viperdb.scripps.edu) is a relational database and a web portal for icosahedral virus capsid structures. Our aim is to provide a comprehensive resource specific to the needs of the virology community, with an emphasis on the description and comparison of derived data from structural and computational analyses of the virus capsids. In the current release, VIPERdb2, we implemented a useful and novel method to represent capsid protein residues in the icosahedral asymmetric unit (IAU) using azimuthal polar orthographic projections, otherwise known as Φ–Ψ (Phi–Psi) diagrams. In conjunction with a new Application Programming Interface (API), these diagrams can be used as a dynamic interface to the database to map residues (categorized as surface, interface and core residues) and identify family wide conserved residues including hotspots at the interfaces. Additionally, we enhanced the interactivity with the database by interfacing with web-based tools. In particular, the applications Jmol and STRAP were implemented to visualize and interact with the virus molecular structures and provide sequence–structure alignment capabilities. Together with extended curation practices that maintain data uniformity, a relational database implementation based on a schema for macromolecular structures and the APIs provided will greatly enhance the ability to do structural bioinformatics analysis of virus capsids.

A 20-ns molecular dynamics simulation of Ca(2+)-calmodulin (CaM) in explicit solvent is described. Within 5 ns, the extended crystal structure adopts a compact shape similar in dimension to complexes of CaM and target peptides but with a substantially different orientation between the N- and C-terminal domains. Significant interactions are observed between the terminal domains in this compact state, which are mediated through the same regions of CaM that bind to target peptides derived from protein kinases and most other target proteins. The process of compaction is driven by the loss of helical structure in two separate regions between residues 75-79 and 82-86, the latter being driven by unfavorable electrostatic interactions between acidic residues. In the first 5 ns of the simulation, a substantial number of contacts are observed between the first helix of the N-terminal domain and residues 74-77 of the central linker. These contacts are correlated with the closing of the second EF-hand, indicating a mechanism by which they can lower calcium affinity in the N-terminal domain.

Molecular-dynamics simulations covering 30 ns of both a natural and a synthetic antimicrobial peptide in the presence of a zwitterionic lipid bilayer were performed. In both simulations, copies of the peptides were placed in an alpha-helical conformation on either side of the bilayer about 10 A (1 A=0.1 nm) from the interface, with either the hydrophobic or the positively charged face of the helix directed toward the bilayer surface. The degree of peptide-lipid interaction was dependent on the starting configuration: surface binding and subsequent penetration of the bilayer was observed for the hydrophobically oriented peptides, while the charge-oriented peptides demonstrated at most partial surface binding. Aromatic residues near the N-termini of the peptides appear to play an important role in driving peptide-lipid interactions. A correlation between the extent of peptide-lipid interactions and helical stability was observed in the simulations. Insertion of the peptides into the bilayer caused a dramatic increase in the lateral area per lipid and decrease in the bilayer thickness, resulting in substantial disordering of the lipid chains. Results from the simulations are consistent with early stages of proposed mechanisms for the lytic activity of antimicrobial peptides. In addition to these 'free' simulations, 25 ns simulations were carried out with the peptides constrained at three different distances relative to the bilayer interface. The constraint forces are in agreement with the extent of peptide-bilayer insertion observed in the free simulations.

VIPERdb () is a database for icosahedral virus capsid structures. Our aim is to provide a comprehensive resource specific to the needs of the structural virology community, with an emphasis on the description and comparison of derived data from structural and energetic analyses of capsids. A relational database implementation based on a schema for macromolecular structure makes the data highly accessible to the user, allowing detailed queries at the atomic level. Together with curation practices that maintain data uniformity, this will facilitate structural bioinformatics studies of virus capsids. User friendly search, visualization and educational tools on the website allow both structural and derived data to be examined easily and extensively. Links to relevant literature, sequence and taxonomy databases are provided for each entry.