Biomedical subjects

Christina L Vizcarra

Publications and source records attributed to Christina L Vizcarra.

3 recordsLinked to original sources

PubMed2006

Computationally designed libraries of fluorescent proteins evaluated by preservation and diversity of function.

To determine which of seven library design algorithms best introduces new protein function without destroying it altogether, seven combinatorial libraries of green fluorescent protein variants were designed and synthesized. Each was evaluated by distributions of emission intensity and color compiled from measurements made in vivo. Additional comparisons were made with a library constructed by error-prone PCR. Among the designed libraries, fluorescent function was preserved for the greatest fraction of samples in a library designed by using a structure-based computational method developed and described here. A trend was observed toward greater diversity of color in designed libraries that better preserved fluorescence. Contrary to trends observed among libraries constructed by error-prone PCR, preservation of function was observed to increase with a library's average mutation level among the four libraries designed with structure-based computational methods.

Combinatorial Chemistry Techniques↗

PubMed2005

Electrostatics in computational protein design.

Catalytic activity and protein-protein recognition have proven to be significant challenges for computational protein design. Electrostatic interactions are crucial for these and other protein functions, and therefore accurate modeling of electrostatics is necessary for successfully advancing protein design into the realm of protein function. This review focuses on recent progress in modeling electrostatic interactions in computational protein design, with particular emphasis on continuum models.

Computer Simulation↗

PubMed2005

One- and two-body decomposable Poisson-Boltzmann methods for protein design calculations.

Successfully modeling electrostatic interactions is one of the key factors required for the computational design of proteins with desired physical, chemical, and biological properties. In this paper, we present formulations of the finite difference Poisson-Boltzmann (FDPB) model that are pairwise decomposable by side chain. These methods use reduced representations of the protein structure based on the backbone and one or two side chains in order to approximate the dielectric environment in and around the protein. For the desolvation of polar side chains, the two-body model has a 0.64 kcal/mol RMSD compared to FDPB calculations performed using the full representation of the protein structure. Screened Coulombic interaction energies between side chains are approximated with an RMSD of 0.13 kcal/mol. The methods presented here are compatible with the computational demands of protein design calculations and produce energies that are very similar to the results of traditional FDPB calculations.

Poisson Distribution↗