Learn More
We have recently completed a full re-architecturing of the ROSETTA molecular modeling program, generalizing and expanding its existing functionality. The new architecture enables the rapid prototyping of novel protocols by providing easy-to-use interfaces to powerful tools for molecular modeling. The source code of this rearchitecturing has been released as(More)
Protein-protein interactions, which form the basis for most cellular processes, result in the formation of protein interfaces. Believing that the local shape of proteins is crucial, we take a geometric approach and present a definition of an interface surface formed by two or more proteins. We also present an algorithm and study the geometric and(More)
The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike(More)
A lens with a graded refractive index is required for vision in aquatic animals with camera-type eyes. This optical design entails a radial gradient of protein density, with low density in external layers and high density in internal layers. To maintain the optical stability of the eye, different material properties are required for proteins in different(More)
Drugs and other chemical compounds are often modeled as polygonal shapes, where each vertex represents an atom of the molecule, and covalent bonds between atoms are represented by edges between the corresponding ver-tices. This polygonal shape derived from a chemical compound is often called its molecular graph, and can be a path, a tree, or in general a(More)
PURPOSE OF REVIEW We review structural information on the native HIV envelope trimer and the known epitopes for broadly neutralizing antibodies and discuss how this structural information should guide the design of more effective immunogens. RECENT FINDINGS Recent epitope mapping of HIV-positive sera demonstrates that the immune system is able to mount a(More)
The manipulation of protein backbone structure to control interaction and function is a challenge for protein engineering. We integrated computational design with experimental selection for grafting the backbone and side chains of a two-segment HIV gp120 epitope, targeted by the cross-neutralizing antibody b12, onto an unrelated scaffold protein. The final(More)
Broadly cross-reactive monoclonal antibodies define epitopes for vaccine development against HIV and other highly mutable viruses. Crystal structures are available for several such antibody-epitope complexes, but methods are needed to translate that structural information into immunogens that re-elicit similar antibodies. We describe a general computational(More)
Evaluating the quality of experimentally determined protein structural models is an essential step toward identifying potential errors and guiding further structural refinement. Herein, we report the use of proton local density as a sensitive measure to assess the quality of nuclear magnetic resonance (NMR) structures. Using 256 high-resolution crystal(More)
Complex N-glycans flank the receptor binding sites of the outer domain of HIV-1 gp120, ostensibly forming a protective "fence" against antibodies. Here, we investigated the effects of rebuilding this fence with smaller glycoforms by expressing HIV-1 pseudovirions from a primary isolate in a human cell line lacking N-acetylglucosamine transferase I (GnTI),(More)