-a multiple histidine post-translational-modification (PTM) prediction server based on protein sequences using convolution neural network: a case study on mass spectroscopy data.

Computational characterization of multiple Histidine (His) post-translational-modifications (PTM) at enzyme active sites complements tedious experimental characterization in proteins-of-unknown-functions (PUFs) and domain-of-unknown-functions (DUFs). There are only a handful of Histidine-PTM-prediction-tools and those also annotate only a single function. Here, we addressed the problem using artificial neural networks on functional histidine dataset curated from enzyme (protein) sequences available in UniProt database (sample size  = 1584).

Decoding the 'Fifth' Nucleotide: Impact of RNA Pseudouridylation on Gene Expression and Human Disease.

Cellular RNAs, both coding and noncoding are adorned by > 100 chemical modifications, which impact various facets of RNA metabolism and gene expression. Very often derailments in these modifications are associated with a plethora of human diseases. One of the most oldest of such modification is pseudouridylation of RNA, wherein uridine is converted to a pseudouridine (Ψ) via an isomerization reaction.

Covalent Capture of Collagen Triple Helices Using Lysine-Aspartate and Lysine-Glutamate Pairs.

Collagen mimetic peptides (CMPs) self-assemble into a triple helix reproducing the most fundamental aspect of the collagen structural hierarchy. They are therefore important for both further understanding this complex family of proteins and use in a wide range of biomaterials and biomedical applications. CMP self-assembly is complicated by a number of factors which limit the use of CMPs including their slow rate of folding, relatively poor monomer-trimer equilibrium, and the large number of competing species possible in heterotrimeric helices.

Chain alignment of collagen I deciphered using computationally designed heterotrimers.

The most abundant member of the collagen protein family, collagen I (also known as type I collagen; COL1), is composed of one unique (chain B) and two similar (chain A) polypeptides that self-assemble with one amino acid offset into a heterotrimeric triple helix. Given the offset, chain B can occupy either the leading (BAA), middle (ABA) or trailing (AAB) position of the triple helix, yielding three isomeric biomacromolecules with different protein recognition properties. Despite five decades of intensive research, there is no consensus on the position of chain B in COL1.

Drug-triggered and cross-linked self-assembling nanofibrous hydrogels.

Self-assembly of multidomain peptides (MDP) can be tailored to carry payloads that modulate the extracellular environment. Controlled release of growth factors, cytokines, and small-molecule drugs allows for unique control of in vitro and in vivo responses. In this study, we demonstrate this process of ionic cross-linking of peptides using multivalent drugs to create hydrogels for sustained long-term delivery of drugs.

Highly angiogenic peptide nanofibers.

Major limitations of current tissue regeneration approaches using artificial scaffolds are fibrous encapsulation, lack of host cellular infiltration, unwanted immune responses, surface degradation preceding biointegration, and artificial degradation byproducts. Specifically, for scaffolds larger than 200-500 μm, implants must be accompanied by host angiogenesis in order to provide adequate nutrient/waste exchange in the newly forming tissue. In the current work, we design a peptide-based self-assembling nanofibrous hydrogel containing cell-mediated degradation and proangiogenic moieties that specifically address these challenges.

Comparative NMR analysis of collagen triple helix organization from N- to C-termini.

The collagen triple helix consists of three supercoiled solvent-exposed polypeptide chains, and by dry weight it is the most abundant fold in mammalian tissues. Many factors affecting the structure and stability of collagen have been determined through the use of short synthetically prepared peptides, generally called collagen-mimetic peptides (CMPs). NMR (nuclear magnetic resonance spectroscopy) investigations into the molecular structure of CMPs have suffered from large amounts of signal overlap and degeneracy because of collagen's repetitive primary sequence, the close and symmetric packing of the three chains and the identical peptide sequences found in homotrimers.

Keplerate cluster (Mo-132) mediated electrostatic assembly of nanoparticles.

The electrostatic assembly between a series of differently charged Mo-132-type Keplerates present in the compounds (NH4)42[{(Mo(VI))Mo(VI)5O21(H2O)6}12 {Mo(V)2O4(CH3COO)}30].ca. {300 H2O+10 CH3COONH4} (Mo-132a), (NH4)72-n[{(H2O)81-n+(NH4)n} {(Mo(VI))Mo(VI)5O21(H2O)6}12 {Mo(V)2O4(SO4)}30].

Rational design of a non-canonical "sticky-ended" collagen triple helix.

In a canonical collagen triple helix, three peptides self-assemble into a supercoiled motif with a one-amino-acid offset between the peptide chains. Design of triple helices that contain more than one residue offset is lucrative, as it leaves the non-covalent interactions unsatisfied at the termini and renders the termini "sticky" to further self-assemble into collagen-like nanofibers. Here we use lysine-glutamate axial salt-bridges to design a heterotrimeric collagen triple helix, ABC-1, containing a non-canonical offset of four residues between the peptide chains.

A nanostructured synthetic collagen mimic for hemostasis.

Collagen is a major component of the extracellular matrix and plays a wide variety of important roles in blood clotting, healing, and tissue remodeling. Natural, animal derived, collagen is used in many clinical applications but concerns exist with respect to its role in inflammation, batch-to-batch variability, and possible disease transfection. Therefore, development of synthetic nanomaterials that can mimic the nanostructure and properties of natural collagen has been a heavily pursued goal in biomaterials.

Pairwise interactions in collagen and the design of heterotrimeric helices.

A comprehensive survey of single amino acid substitutions in the canonical Xaa-Yaa-Gly repeat has laid the ground work for our understanding of the collagen triple helix. Building upon this foundation requires understanding pairwise amino acid interactions which will allow us to prepare heterotrimeric helices with great specificity in addition to an overall improved control over helix structure and stability. Furthermore, detailed studies on these interactions will help us understand collagen's n structure, assembly mechanism and stability.

Hydroxyproline-free single composition ABC collagen heterotrimer.

Hydroxyproline plays a major role in stabilizing collagenous domains in eukaryotic organisms. Lack of this modification is associated with significant lowering in the thermal stability of the collagen triple helix and may also affect fibrillogenesis and folding of the peptide chains. In contrast, even though bacterial collagens lack hydroxyproline, their thermal stability is comparable to that of fibrillar collagen.

Simultaneous control of composition and register of an AAB-type collagen heterotrimer.

Control over composition and register of the peptide chains in AAB-type collagen mimetic heterotrimers is critical in developing systems that show fidelity to native collagen. However, their design is challenging due to the eight competing states possible for a mixture of nonidentical peptides A and B. Interpeptide salt-bridges have been used previously as keystone interactions to bias the population of competing states to favor a target heterotrimer.

Rational design of single-composition ABC collagen heterotrimers.

Design of heterotrimeric ABC collagen triple helices is challenging due to the large number of competing species that may be formed. Given the required one amino acid stagger between adjacent peptide strands in this fold, a ternary mixture of peptides can form as many as 27 triple helices with unique composition or register. Previously we have demonstrated that electrostatic interactions can be used to bias the helix population toward a desired target.