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Minimal Perturbation (minimal + perturbation)

Distribution by Scientific Domains

Chemistry	75%

Selected Abstracts

g_membed: Efficient insertion of a membrane protein into an equilibrated lipid bilayer with minimal perturbation

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 11 2010
Maarten G. Wolf
Abstract To efficiently insert a protein into an equilibrated and fully hydrated membrane with minimal membrane perturbation we present a computational tool, called g_membed, which is part of the Gromacs suite of programs. The input consists of an equilibrated membrane system, either flat or curved, and a protein structure in the right position and orientation with respect to the lipid bilayer. g_membed first decreases the width of the protein in the xy -plane and removes all molecules (generally lipids and waters) that overlap with the narrowed protein. Then the protein is grown back to its full size in a short molecular dynamics simulation (typically 1000 steps), thereby pushing the lipids away to optimally accommodate the protein in the membrane. After embedding the protein in the membrane, both the lipid properties and the hydration layer are still close to equilibrium. Thus, only a short equilibration run (less then 1 ns in the cases tested) is required to re-equilibrate the membrane. Its simplicity makes g_membed very practical for use in scripting and high-throughput molecular dynamics simulations. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010 [source]

Some fundamental aspects of building protein structures from fragment libraries

PROTEIN SCIENCE, Issue 6 2004
J. Bradley Holmes
Abstract We have investigated some of the basic principles that influence generation of protein structures using a fragment-based, random insertion method. We tested buildup methods and fragment library quality for accuracy in constructing a set of known structures. The parameters most influential in the construction procedure are bond and torsion angles with minor inaccuracies in bond angles alone causing >6 Å C,RMSD for a 150-residue protein. Idealization to a standard set of values corrects this problem, but changes the torsion angles and does not work for every structure. Alternatively, we found using Cartesian coordinates instead of torsion angles did not reduce performance and can potentially increase speed and accuracy. Under conditions simulating ab initio structure prediction, fragment library quality can be suboptimal and still produce near-native structures. Using various clustering criteria, we created a number of libraries and used them to predict a set of native structures based on nonnative fragments. Local C,RMSD fit of fragments, library size, and takeoff/landing angle criteria weakly influence the accuracy of the models. Based on a fragment's minimal perturbation upon insertion into a known structure, a seminative fragment library was created that produced more accurate structures with fragments that were less similar to native fragments than the other sets. These results suggest that fragments need only contain native-like subsections, which when correctly overlapped, can recreate a native-like model. For fragment-based, random insertion methods used in protein structure prediction and design, our findings help to define the parameters this method needs to generate near-native structures. [source]

Designed protein G core variants fold to native-like structures: Sequence selection by ORBIT tolerates variation in backbone specification

PROTEIN SCIENCE, Issue 2 2001
Scott A. Ross
Abstract The solution structures of two computationally designed core variants of the ,1 domain of streptococcal protein G (G,1) were solved by 1H NMR methods to assess the robustness of amino acid sequence selection by the ORBIT protein design package under changes in protein backbone specification. One variant has mutations at three of 10 core positions and corresponds to minimal perturbations of the native G,1 backbone. The other, with mutations at six of 10 positions, was calculated for a backbone in which the separation between G,1's ,-helix and ,-sheet was increased by 15% relative to native G,1. Exchange broadening of some resonances and the complete absence of others in spectra of the sixfold mutant bespeak conformational heterogeneity in this protein. The NMR data were sufficiently abundant, however, to generate structures of similar, moderately high quality for both variants. Both proteins adopt backbone structures similar to their target folds. Moreover, the sequence selection algorithm successfully predicted all core ,1 angles in both variants, five of six ,2 angles in the threefold mutant and four of seven ,2 angles in the sixfold mutant. We conclude that ORBIT calculates sequences that fold specifically to a geometry close to the template, even when the template is moderately perturbed relative to a naturally occurring structure. There are apparently limits to the size of acceptable perturbations: In this study, the larger perturbation led to undesired dynamic behavior. [source]

Evolution of the reverse link of CDMA-based systems to support high-speed data

BELL LABS TECHNICAL JOURNAL, Issue 3 2002
Nandu Gopalakrishnan
Development of an upcoming release of the CDMA2000* family of standards is expected to focus on enhancing the reverse link (RL) operation to support high-speed packet data applications. The challenge is to design a system that yields substantial throughput gain while causing only minimal perturbations to the existing standard. We are proposing a system that evolves features already present in the CDMA2000 Release B and IS-856 (1xEV-DO) standards and reuses concepts and capabilities that have been introduced for high-speed packet data support on the forward link (FL) in Release C of the CDMA2000 standard. The RL of Release C of the CDMA2000 standard supports a relatively slow scheduled operation of this link using signaling messages. Scheduling with shorter latencies can be achieved by moving this functionality to the physical layer. Concurrently, both the FL and RL channel conditions may be tracked, and users may be scheduled based on this knowledge. To further manage the power and bandwidth cost on the FL, that is, of scheduling users' transmissions on the RL, the mobile station (MS) is permitted to operate in either a scheduled mode or an autonomous mode. A capability is provided for the MS station to switch the mode of operation. Performance impact of, and gain from, some of the system features is characterized through simulation results. © 2003 Lucent Technologies Inc. [source]