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We investigate the application of torsion angle molecular dynamics (TAMD) to augment conformational sampling of peptides and proteins. Interesting conformational changes in proteins mainly involve torsional degrees of freedom. Carrying out molecular dynamics in torsion space does not only explicitly sample the most relevant degrees of freedom, but also allows larger integration time steps with elimination of the bond and angle degrees of freedom. However, the covalent geometry needs to be fixed during internal coordinate dynamics, which can introduce severe distortions to the underlying potential surface in the extensively parameterized modern Cartesian-based protein force fields. A “projection” approach (Katritch et al. J Comput Chem 2003, 24, 254–265) is extended to construct an accurate internal coordinate force field (ICFF) from a source Cartesian force field. Torsion crossterm corrections constructed from local molecular fragments, together with softened van der Waals and electrostatic interactions, are used to recover the potential surface and incorporate implicit bond and angle flexibility. MD simulations of dipeptide models demonstrate that full flexibility in both the backbone φ/ψ and side chain χ1 angles are virtually restored. The efficacy of TAMD in enhancing conformational sampling is then further examined by folding simulations of small peptides and refinement experiments of protein NMR structures. The results show that an increase of several fold in conformational sampling efficiency can be reliably achieved. The current study also reveals some complicated intrinsic properties of internal coordinate dynamics, beyond energy conservation, that can limit the maximum size of the integration time step and thus the achievable gain in sampling efficiency. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1565–1578, 2005 [ABSTRACT FROM AUTHOR]

Stability and performance of the filter diagonalization method (FDM) for harmonic inversion [i.e., fitting a time signal by C(t)=∑[sub k] d[sub k]e[sup -itω[sub k]]] of noisy data are examined. Although FDM is capable to extract accurately the parameters of narrow spectral peaks, in the presence of broad peaks (or strong background spectrum) and noise, the FDM ersatz spectrum, i.e., I(ω)=∑[sub k]d[sub k]/(ω[sub k]-ω), maybe distorted in some regions and be sensitive to the FDM parameters, such as window size, window position, etc. Some simple hybrid methods, that can correct the ersatz spectrum, are discussed. However, a more consistent approach, the multiscale FDM, is introduced to solve the instability problem, in which some coarse basis vectors describing (in low resolution) the global behavior of the spectrum are added to the narrow band Fourier basis. The multiscale FDM is both stable and accurate, even when the total size of the basis (i.e., the number of coarse plus narrow band basis vectors) used is much smaller than what would previously be considered as necessary for FDM. This, in turn, significantly reduces the computation cost. Extension of the 1D multiscale FDM to a multidimensional case is also presented. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

An abstract of the article "Peptide and Protein Folding and Conformational Equilibria: Theoretical Treatment of Electrostatics and Hydrogen Bonding With Implicit Solvent Models," by Wonpil Im and colleagues is presented.