C J Carrillo | PubMed Health

PubMed1999

Integrating computation and visualization for biomolecular analysis: an example using python and AVS.

One of the challenges in biocomputing is to enable the efficient use of a wide variety of fast-evolving computational methods to simulate, analyze, and understand the complex properties and interactions of molecular systems. Our laboratory investigates several areas including molecular visualization, protein-ligand docking, protein-protein docking, molecular surfaces, and the derivation of phenomenological potentials. In this paper we present an approach based on the Python programming language to achieve a high level of integration between these different computational methods and our primary visualization system AVS. This approach removes many limitations of AVS while increasing dramatically the inter-operability of our computational tools. Several examples are shown to illustrate how this approach enables a high level of integration and inter-operability between different tools, while retaining modularity and avoiding the creation of a large monolithic package that is difficult to extend and maintain.

Capsid↗

PubMed1992

Mutants of complement component C3 cleaved by the C4-specific C1-s protease.

To identify some of the structural features determining specific protease recognition of complement components C3 and C4, we used site-specific mutagenesis to construct mutants of murine C3 that are cleaved by the C4-specific C1-s protease. Insertion of three amino acid residues corresponding to residues at the C1-s cleavage site of human C4 into murine C3 at the analogous C3 convertase cleavage site was adequate to render the mutant protein susceptible to C1-s cleavage. In addition, insertion of C3-specific residues at the same site or introduction of the C4-specific residues as substitutions rather than as an insertion also rendered the site susceptible to cleavage, but with 10- to 50-fold lower efficiencies, and insertion of even a single amino acid residue affected recognition by C1-s. Finally, insertion of amino acid residues into mC3 partially inhibited cleavage by the alternative-pathway C3 convertase, with insertion of C3- or C4-specific residues giving about the same level of inhibition. A simple interpretation of these data is that C1-s cleavage is dependent primarily on steric accessibility and on recognition of specific amino acid residues at the cleavage site, whereas C3 convertase cleavage is dependent primarily on specific interactions distal to the cleavage site, with only relatively weak, non-C3-specific interactions at the cleavage site itself.

Amino Acid Sequence↗