Anisotropic Network Analysis of Open/Closed HCN4 Channel Advocates Asymmetric Subunit Cooperativity in cAMP Modulation of Gating.

Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are opened in an allosteric manner by membrane hyperpolarization and cyclic nucleotides such as cAMP. Because of conflicting reports from experimental studies on whether cAMP binding to the four available binding sites in the channel tetramer operates cooperatively in gating, we employ here a computational approach as a promising route to examine ligand-induced conformational changes after binding to individual sites. By combining an elastic network model (ENM) with linear response theory (LRT) for modeling the apo-holo transition of the cyclic nucleotide-binding domain (CNBD) in HCN channels, we observe a distinct pattern of cooperativity matching the "positive-negative-positive" cooperativity reported from functional studies.

Biotite: new tools for a versatile Python bioinformatics library.

Background: Biotite is a program library for sequence and structural bioinformatics written for the Python programming language. It implements widely used computational methods into a consistent and accessible package. This allows for easy combination of various data analysis, modeling and simulation methods.

Adding hydrogen atoms to molecular models via fragment superimposition.

Background: Most experimentally determined structures of biomolecules lack annotated hydrogen positions due to their low electron density. However, thorough structure analysis and simulations require knowledge about the positions of hydrogen atoms. Existing methods for their prediction are either limited to a certain range of molecules or only work effectively on small compounds.

A Spatial and Functional Interaction of a Heterotetramer Survivin-DNA-PKcs Complex in DNA Damage Response.

Substantial evidence has shown that overexpression of the inhibitor of apoptosis protein (IAP) survivin in human tumors correlates significantly with treatment resistance and poor patient prognosis. Survivin serves as a radiation resistance factor that impacts the DNA damage response by interacting with DNA-dependent protein kinase (DNA-PKcs). However, the complexity, molecular determinants, and functional consequences of this interrelationship remain largely unknown.

Substitution matrix based color schemes for sequence alignment visualization.

Background: Visualization of multiple sequence alignments often includes colored symbols, usually characters encoding amino acids, according to some (physical) properties, such as hydrophobicity or charge. Typically, color schemes are created manually, so that equal or similar colors are assigned to amino acids that share similar properties. However, this assessment is subjective and may not represent the similarity of symbols very well.

Biotite: a unifying open source computational biology framework in Python.

Background: As molecular biology is creating an increasing amount of sequence and structure data, the multitude of software to analyze this data is also rising. Most of the programs are made for a specific task, hence the user often needs to combine multiple programs in order to reach a goal. This can make the data processing unhandy, inflexible and even inefficient due to an overhead of read/write operations.