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Biomedical subjects

Soonmin Jang

Publications and source records attributed to Soonmin Jang.

8 recordsLinked to original sources
PubMed2007

Direct folding simulation of alpha-helices and beta-hairpins based on a single all-atom force field with an implicit solvation model.

Recently, we have shown that a modified energy model based on the param99 force field with the generalized Born (GB) solvation model produces reliable free energy landscapes of mini-proteins with a betabetaalpha motif (BBA5, 1FSD, and 1PSV), with the native structures of the mini-proteins located in their lowest free energy minimum states. One of the main features in the modified energy model is a significant improvement for more balanced treatments of alpha and beta strands in proteins. In this study, using the replica exchange molecular dynamics (REMD) simulation method with this new force field, we have carried out extensive ab initio folding studies of several well-known peptides with alpha or beta strands (C-peptide, EK-peptide, le0q, and gbl). Starting from fully extended conformations as the initial conditions, all of the native-like structures of the target peptides were successfully identified by REMD, with reasonable representations of free energy surfaces. The present simulation results with the modified energy model are consistent with experiments, demonstrating an extended applicability of the energy model to folding studies of a variety of alpha-helices, beta-strands, and alpha/beta proteins.

Amino Acid Sequence↗
PubMed2006

Theoretical investigation of the photoinitiated folding of HP-36.

A computational model was developed to examine the phototriggered folding of a caged protein, a protein modified with an organic photolabile cross-linker. Molecular dynamics simulations of the modified 36-residue fragment of subdomain B of chicken villin head piece with a photolabile linker were performed, starting from both the caged and the uncaged structures. Construction of a free-energy landscape, based on principal components as well as on radius of gyration versus root-mean-square deviation, and circular dichroism calculations were employed to characterize folding behavior and structures. The folded structures observed in the molecular dynamics trajectories were found to be similar to that of the wild-type protein, in agreement with the published experimental results. The free-energy landscapes of the modified and wild-type proteins have similar topology, suggesting common thermodynamic/kinetic behavior. The existence of small differences in the free-energy surface of the modified protein from that of the native protein, however, indicates subtle differences in the folding behavior.

Animals↗
PubMed2006

Free energy surfaces of miniproteins with a betabetaalpha motif: replica exchange molecular dynamics simulation with an implicit solvation model.

Designed miniproteins with a betabetaalpha motif, such as BBA5, 1FSD, and 1PSV can serve as a benchmark set to test the validity of all-atom force fields with computer simulation, because they contain all the basic structural elements in protein folding. Unfortunately, it was found that the standard all-atom force fields with the generalized Born (GB) implicit solvation model tend to produce distorted free energy surfaces for the betabetaalpha proteins, not only because energetically those proteins need to be described by more balanced weights of the alpha- and beta-strands, but also because the GB implicit solvation model suffers from overestimated salt bridge effects. In an attempt to resolve these problems, we have modified one of the standard all-atom force fields in conjunction with the GB model, such that each native state of the betabetaalpha proteins is in its free energy minimum state with reasonable energy barriers separating local minima. With this modified energy model, the free energy contour map in each protein was constructed from the replica exchange molecular dynamics REMD simulation. The resulting free energy surfaces are significantly improved in comparison with previous simulation results and consistent with general views on small protein folding behaviors with realistic topology and energetics of all three proteins.

Calorimetry↗
PubMed2006

Amyloid beta-peptide oligomerization in silico: dimer and trimer.

Soluble oligomers of Alzheimer's amyloid beta protein (Abeta) may act as effectors of neurotoxicity in early stages of Alzheimer's disease. Detailed information about the structure of Abeta in atomistic level and the dynamics of assembly of monomeric Abeta into oligomeric structures is rather elusive. We have performed replica exchange molecular dynamics (REMD) simulations on the formation of the dimer and trimer of Abeta10-35 peptide. We have observed spontaneous formation of several basic structural units that may act as a template or an intermediate for further aggregation of Alzheimer's Abeta protein. Various conformers, including interlocking structures of experimentally known bend double beta strands, are identified.

Alzheimer Disease↗
PubMed2003

Ab initio folding of helix bundle proteins using molecular dynamics simulations.

We have demonstrated that ab initio fast folding simulations at 400 K using a GB implicit solvent model with an all-atom based force field can describe the spontaneous formation of nativelike structures for the 36-residue villin headpiece and the 46-residue fragment B of Staphylococcal protein A. An implicit solvent model combined with high-temperature MD makes it possible to perform direct folding simulations of small- to medium-sized proteins by reducing the computational requirements tremendously. In the early stage of folding of the villin headpiece and protein A, initial hydrophobic collapse and rapid formation of helices were found to play important roles. For protein A, the third helix forms first in the early stage of folding and exhibits higher stability. The free energy profiles calculated from the folding simulations suggested that both of the helix-bundle proteins show a two-state thermodynamic behavior and protein A exhibits rather broad native basins.

Computer Simulation↗
PubMed2003

Replica-exchange method using the generalized effective potential.

We propose an effective scheme for fast conformational searches by combining the replica exchange method (REM) with the generalized effect potential concept. The present method introduces the "q" value from the effective potential as a coupling parameter. It is found that the new method not only requires a much smaller number of replicas than the conventional REM, but also makes it possible to perform effective conformational sampling of complex systems with correct distributions maintained. The advantage of the present method has been demonstrated with in vacuo alanine dipeptide using a molecular dynamics simulation.

Computer Simulation↗
PubMed2002

Molecular dynamics study of peptides in implicit water: ab initio folding of beta-hairpin, beta-sheet, and beta beta alpha-motif.

In this communication, we have demonstrated that molecular dynamics simulations using a GB implicit solvation model with the all-atom based force field (CHARMM19) can describe the spontaneous folding of small peptides in aqueous solution. The native structures of peptides with various structural motifs (beta-hairpin, beta-sheet, and betabetaalpha-moiety) were successfully predicted within reasonable time scales by MD simulations at moderately elevated temperatures. It is expected that the present simulations provide further insight into mechanism/pathways of the peptide folding.

Amino Acid Sequence↗