We propose a general theory of cooperativity between transmembrane receptors of a cell. Based on a conformation-dependent interaction between nearest-neighboring receptors, the sensitive signalling and the enhancement of clustering, or oligomerization, are explained as two responses to ligand binding. In this model, ligand binding shifts the energy difference between the two conformational stat...

It is an outstanding problem to clarify how the RNA sequence is related to its structure and biological functions. We developed a simplified definition of a metric for tree representation of RNA secondary structures and analyzed the conformational energy landscapes of human spliceosomal snRNAs. We discuss the structural properties of the biological sequence by calculating the conformational ene...

Vitamin D Receptor (VDR) belongs to the nuclear receptor (NR) superfamily. Whereas the structure of the ligand binding domain (LBD) of VDR has been determined in great detail, the role of its amino acid residues in stabilizing the structure and ligand triggering conformational change is still under debate. There are 13 α-helices and one β-sheet in the VDR LBD and they form a three-layer sandwic...

Conformational change in protein-ligand complexes is widely modeled, but the protein accommodation expected on binding a congeneric series of ligands has received less attention. Given their use in medicinal chemistry, there are surprisingly few substantial series of congeneric ligand complexes in the Protein Data Bank (PDB). Here we determine the structures of eight alkyl benzenes, in single-m...

The mammalian high mobility group protein HMGA2 contains three DNA binding motifs associated with many physiological functions including oncogenesis, obesity, stem cell youth, human height, and human intelligence. In the present paper, trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) has been utilized to study the conformational dynamics of the third DNA binding motif using the "AT...

background and objective: familial hypercholesterolemia (fh) is an autosomal trait, which is caused by mutations in low density lipoprotein receptor (ldlr) gene. fh penetrance is about 100% and worldwide prevalence for heterozygous subjects is almost 1 in 500 and for homozygous 1 in 1,000,000. the patients are at risk of premature coronary heart disease (chd) due to defective ldlr and hence cho...

BACKGROUND The conformational conversion of the host-derived cellular prion protein (PrP(C)) into the disease-associated scrapie isoform (PrP(Sc)) is responsible for the pathogenesis of transmissible spongiform encephalopathies (TSEs). Various single-point mutations in PrP(C)s could cause structural changes and thereby distinctly influence the conformational conversion. Elucidation of the diffe...