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We have completed a molecular dynamics simulation of protein (bovine pancreatic trypsin inhibitor, BPTI) in solution at high pressure (10 kbar). The structural and energetic effects of the application of high pressure to solvated protein are analyzed by comparing the results of the high-pressure simulation with a corresponding simulation at low pressure. The volume of the simulation cell containing one protein molecule plus 2943 water molecules decreases by 24.7% at high pressure. This corresponds to a compressibility for the protein solution of beta = 1.8 x 10(-2) kbar-1. The compressibility of the protein is estimated to be about one-tenth that of bulk water, while the protein hydration layer water is found to have a greater compressibility as compared to the bulk, especially for water associated with hydrophobic groups. The radius of gyration of BPTI decreases by 2% and there is a one third decrease in the protein backbone atomic fluctuations at high pressure. We have analyzed pressure effects on the hydration energy of the protein. The total hydration energy is slightly (4%) more favorable at high pressure even though the surface accessibility of the protein has decreased by a corresponding amount. Large pressure-induced changes in the structure of the hydration shell are observed. Overall, the solvation shell waters appear more ordered at high pressure; the pressure-induced ordering is greatest for nonpolar surface groups. We do not observe evidence of pressure-induced unfolding of the protein over the 100-ps duration of the high-pressure simulation. This is consistent with the results of high-pressure optical experiments on BPTI.(ABSTRACT TRUNCATED AT 250 WORDS)

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Three useful procedures for estimating the thermodynamic stability and charge distribution of moderately complex unknown species are illustrated by the successive nitration of cubane. (1) Five different, but interrelated, energy criteria are employed, which leads to mutually supportive conclusions that overcome deficiencies in any one of the single measures. (2) Mulliken charge and overlap populations can lead to correct bond strength trends if appropriate averaging over bond types is carried out. (3) Lewis—Langmuir atomic charges, an interpolation between the formal charges of Lewis dot structures and oxidation numbers which does not require use of computers, provides atomic charges similar to those from ab initio, wavefunctions. The simplicity of this scheme aids in identifying the chemical and topological origin of molecular charge distributions. Ab initio, calculations for the strain energies and heats of reaction for four different reaction sequences are reported, together with Mulliken atomic charges and overlap populations for the nitrocubanes. Trends in these measures suggest that hexa‐ and octa‐nitrocubane are thermodynamically stable species.