Biomedical subjects

Seokmin Shin

Publications and source records attributed to Seokmin Shin.

8 recordsLinked to original sources

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

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↗

PubMed2006

ChimerDB--a knowledgebase for fusion sequences.

Chromosome translocation and gene fusion are frequent events in the human genome and are often the cause of many types of tumor. ChimerDB is the database of fusion sequences encompassing bioinformatics analysis of mRNA and expressed sequence tag (EST) sequences in the GenBank, manual collection of literature data and integration with other known database such as OMIM. Our bioinformatics analysis identifies the fusion transcripts that have non-overlapping alignments at multiple genomic loci. Fusion events at exon-exon borders are selected to filter out the cloning artifacts in cDNA library preparation. The result is classified into two groups--genuine chromosome translocation and fusion between neighboring genes owing to intergenic splicing. We also integrated manually collected literature and OMIM data for chromosome translocation as an aid to assess the validity of each fusion event. The database is available at http://genome.ewha.ac.kr/ChimerDB/ for human, mouse and rat genomes.

Animals↗

PubMed2005

ECgene: genome-based EST clustering and gene modeling for alternative splicing.

With the availability of the human genome map and fast algorithms for sequence alignment, genome-based EST clustering became a viable method for gene modeling. We developed a novel gene-modeling method, ECgene (Gene modeling by EST Clustering), which combines genome-based EST clustering and the transcript assembly procedure in a coherent and consistent fashion. Specifically, ECgene takes alternative splicing events into consideration. The position of splice sites (i.e., exon-intron boundaries) in the genome map is utilized as the critical information in the whole procedure. Sequences that share any splice sites are grouped together to define an EST cluster in a manner similar to that of the genome-based version of the UniGene algorithm. Transcript assembly is achieved using graph theory that represents the exon connectivity in each cluster as a directed acyclic graph (DAG). Distinct paths along exons correspond to possible gene models encompassing all alternative splicing events. EST sequences in each cluster are subclustered further according to the compatibility with gene structure of each splice variant, and they can be regarded as clone evidence for the corresponding isoform. The reliability of each isoform is assessed from the nature of cluster members and from the minimum number of clones required to reconstruct all exons in the transcript.

Algorithms↗

PubMed2004

ASmodeler: gene modeling of alternative splicing from genomic alignment of mRNA, EST and protein sequences.

Alternative splicing is in important mechanism of modulating gene function and expression which greatly expands transcriptome diversity. ASmodeler is a novel web-based utility that finds gene models including alternative splicing events from genomic alignment of mRNA, EST and protein sequences. User-supplied sequences are aligned against the genome map using the BLAT and SIM4 programs. Resulting exon connectivity is analyzed by applying graph-theoretic methods to build all possible gene models including splice variants. The algorithm essentially combines the genome-based sequence clustering and transcript assembly procedures in a coherent fashion. In addition to the user-supplied sequences, UniGene clusters and many well-known gene predictions such as Genscan, Ensembl and Acembly may be included in gene modeling. The current implementation supports human, mouse and rat genomes. ASmodeler is available at http://genome.ewha.ac.kr/ECgene/ASmodeler/.

Algorithms↗

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↗