: : ABSTRACT

The protein folding problem is considered one of the major computational challenges in computational biology. In most instances the function of proteins and nucleic acids (DNA ad RNA) are associated to the formation of a regular structure. The process by which proteins reach this structure is called protein folding. The development of enhanced sampling methods and the use of parallel computers allow us to study the thermodynamics of biomolecular folding.

I will describe unbiased molecular dynamics simulations of the thermodynamics of folding/unfolding as a function of temperature and pressure for the trp-cage mini protein, Protein A, and for an RNA tetraloop r(gcUUCGgc). These systems contain 20k atoms or less. These simulations are performed standard classical force fields, in explicit solvent models. The simulations reproduce the folded structure within 2 A (or better) of the experimental results. I will describe the P-T phase diagram for trp-cage and the RNA oligomer and show that the trp cage undergoes cold denaturation and pressure denaturation. These simulations demonstrate that, with extensive sampling, molecular simulations can reasonably describe the structure and thermodynamics of biomolecules.

This work is funded by NSF MCB 0543769, DMR 0117792, NIH, and RPI.

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