We present a coarse residue-based computational method to rapidly compute the solution scattering profile from a protein with dynamical fluctuations. The method is built upon a coarse-grained (CG) representation of the protein. This CG representation takes advantage of the intrinsic low-resolution and CG nature of solution scattering data. It allows rapid scattering determination from a large n...

We study a protein-DNA target search model with explicit DNA dynamics applicable to in vitro experiments. We show that the DNA dynamics plays a crucial role for the effectiveness of protein "jumps" between sites distant along the DNA contour but close in three-dimensional space. A strongly binding protein that searches by one-dimensional sliding and jumping alone explores the search space less ...

Antibody affinity is critically important in therapeutic applications, as well as steady state diagnostic assays. Picomolar affinity antibodies, approaching the association limit of protein-protein interactions, have been discovered for highly potent antigens, but even such high-affinity binders have off-rates sufficient to negate therapeutic efficacy. To cross this affinity threshold, antibodi...

A prototype jig to attach a protein crystallization plate to a standard X-ray goniometer has been designed and constructed in partnership with an engineering firm. This allows a low-cost implementation of in situ diffraction using the available home-laboratory X-ray source.

We investigate how a protein's structure influences the rate at which its sequence evolves. Our basic hypothesis is that proteins with highly designable structures (structures that are encoded by many sequences) will evolve more rapidly. Recent theoretical advances argue that structures with a higher density of interresidue contacts are more designable, and we show that high contact density is ...

It is shown that most present empirical prediction algorithms provide information about the conformational states of individual residues, but give little information about the three-dimensional structure of a protein. It is necessary to predict the conformational state of every residue before the resulting structure can serve as a starting conformation to compute the native structure. It is als...

The selective pressure on a protein-coding gene can be measured by comparing silent (synonymous) and replacement (nonsynonymous) substitution rates. Higher replacement than silent rates provide unequivocal evidence for adaptive evolution driven by Darwinian selection. Previous employment of this criterion involved pairwise sequence comparison, averaging rates over time and sequences, resulting ...

The energies of oligopeptide segments of lysozyme are minimized with respect to the dihedral angles of the central residue. As the length of the oligopeptide segment increases, up to a nonapeptide, the low-energy conformation becomes that observed in the x-ray structure in most cases. This finding suggests that, while short-range interactions appear to play the dominant role in determining the ...

Metamorphic proteins such as lymphotactin are a notable exception of the empirical principle that structured natural proteins possess a unique three-dimensional structure. In particular, the human chemokine lymphotactin protein exists in two distinct conformations (one monomeric and one dimeric) under physiological conditions. In this work, we use a C(alpha) Go model to show how this very pecul...