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The application of hierarchical optimization of protein potential-energy landscapes to optimize the UNRES force field using multiple training proteins is reported. The resulting force field trained on a set of four proteins gives good medium-resolution predictions of the structures of most of the alpha- and the alpha + beta-proteins, but still could not handle nontrivial beta-motifs sufficiently well.

The application of the proposed method of hierarchical optimization of the protein energy landscape to optimize the off-lattice united-residue (UNRES) force field using single training proteins is presented. Technical details of the method, including the maintenance of proper secondary structure and a method to classify structure, are described.

The development of proposed method for optimizing potential-energy functions for protein-structure prediction and folding simulations aimed at obtaining hierarchical energy landscapes of the protein chosen to calibrate a force field is presented. The structure of each benchmark protein is described in terms of structural levels, the number of native structural elements increasing in a given order with level number.

Multibody terms pertaining to the correlation between electrostatic interaction in the UNRES force field were reparameterized on relevant model systems. The resultant force field predicted the structures of proteins with alpha and beta structure.

The N-terminal cysteine-rich somatomedin B (SMB) domain of the human glycoprotien vitronectin contains the high-affinity binding sites for plasminogen activator inhibitor-1(PAI-1) and the urokinase receptor (uPAR). The studies demonstrate that the three dimensional structure of the SMB domain is extremely compact and that the disulfide bonds are packed in the center of the domain forming a covalently bonded core.

Deconjugation of ubiquitin from cellular proteins is catalyzed by the deubiquitin hydrolase (DUB) family of enzymes and is an important component of the ubiquitin regulatory system affecting cellular function beyond maintenance of monomeric pools of ubiquitin. UCH-L3 efficiently cleaves small C-terminal amides of ubiquitin.

Calculations of the diabatic energy surfaces of terminally-blocked amino-acid residues were performed at the Moller-Plesset (MP2) ab initio level of theory with the 6-31G(d,p) basis set. It is essential to have high quality potential-energy surfaces to parametrize a coarse-grain force field, and errors in the parent single-residue all-atom energy surfaces propagate to the mean-field surfaces by numerical integration.

Three energy functions were developed to simulate the free energy of proteins from the alpha, beta and alpha/beta structural classes is presented. The study finally uses a simple model system to show that the VMC protocol does not require exhaustive sampling of medium- and high-energy structures in order to optimize the parameters of the potential energy adequately.

The CAS MCSCF/CAS MCQDPT2 ab initio method utilizing the 6-31G* basis set was used to study the 1,4-cycloaddition reactions of singlet oxygen with s-cis-1,3-butadiene to form 3,6-dihydrol[1,2]dioxin and to benzene to form 2,3-dioxabicyclo-[2.2.2]octa-5,7-diene.

The potentials of mean force (PMFs) are determined for systems that have involved the formation of nonpolar dimers composed of methane, ethane, propane, isobutane and neopentane, respectively, in water, by using the TIP3P water model and in vacuo. It is shown that the neopentane dimer is too small to be treated as a macroscopic hydrophobic object.

Study is presented on the modification and parametrization of the united-residue (UNRES) force field for energy-based protein structure prediction and protein folding simulations. Result demonstrates that it is possible to optimize the UNRES force field for canonical simulations using a protein of any type of secondary structure.

Two current methods of global optimization are coupled to produce the Replica-Exchange method together with Monte Carlo-with-Minimization (REMCM). Its performance is compared with each separate component and with other global optimization techniques. REMCM was applied to search the conformational space of coarse grain protein systems described by the UNRES force field. The method consists of several noninteracting copies of Monte Carlo simulation, and minimization was used after every perturbation to enhance the sampling of low-energy conformations. REMCM was applied to five proteins of different topology, and the results were compared to those from other optimization methods, namely Monte Carlo-with-Minimization (MCM), Conformational Space Annealing (CSA), and Conformational Family Monte Carlo (CFMC). REMCM located global minima for four proteins faster and more consistently than either MCM or CFMC, and it converged faster than CSA for three of the five proteins tested. A performance comparison was also carried out between REMCM and the traditional Replica Exchange method (REM) for one protein, with REMCM showing a significant improvement. Moreover, because of its simplicity, REMCM was easy to implement, thereby offering an alternative to other global optimization methods used in protein structure prediction. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1472–1486, 2005 [ABSTRACT FROM AUTHOR]