Search

Globular proteins (GPs) play vital roles in a wide range of biological processes, encompassing enzymatic catalysis and immune responses. Enzymes, among these globular proteins, facilitate biochemical reactions, while others, such as haemoglobin, contribute to essential physiological functions such as oxygen transport. Given the importance of these considerations, accurately identifying Globular proteins is essential. To address the need for precise GP identification, this research introduces an innovative approach that employs a hybrid-based deep learning model called Deep-GP. We generated two datasets based on primary sequences and developed a novel feature descriptor called, Consensus Sequence-based Trisection-Position Specific Scoring Matrix (CST-PSSM). The model training phase involved the application of deep learning techniques, including the bidirectional long short-term memory network (BiLSTM), gated recurrent unit (GRU), and convolutional neural network (CNN). The BiLSTM and CNN were hybridised for ensemble learning. The CST-PSSM-based ensemble model achieved the most accurate predictive outcomes, outperforming other competitive predictors across both training and testing datasets. This demonstrates the potential of harnessing deep learning for precise GB prediction as a robust tool to expedite research, streamline drug discovery, and unveil novel therapeutic targets., (© 2024 The Author(s). IET Systems Biology published by John Wiley & Sons Ltd on behalf of The Institution of Engineering and Technology.)

The phase separation of biomolecules into biomolecular condensates has emerged as a ubiquitous cellular process. Understanding how intrinsically disordered protein sequence controls condensate formation and material properties has provided fundamental biological insights and led to the development of functional synthetic condensates. While these studies provide a valuable framework to understand subcellular organization via phase separation they have largely ignored the presence of folded domains and their impact on condensate properties. We set out to determine how the distribution of sticker interactions across a globular protein contributes to rheological properties of condensates and to what extent globular protein-containing condensates differ from those formed from two disordered components. We designed three variants of green fluorescent protein with different charge patterning and used dynamic light scattering microrheology to measure the viscoelastic spectrum of coacervates formed with poly-lysine over a timescale of 10 -6 to 10 seconds, elucidating the response of protein condensates in this range for the first time. We further showed that the phase behavior and rheological characteristics of the condensates varied as a function of both protein charge distribution and polymer/protein ratio, behavior that was distinct to condensates formed with folded domains. Together, this work enhances our fundamental understanding of dynamic condensed biomaterials across biologically relevant length- and time-scales., Competing Interests: The authors declare the following competing financial interest(s): A. C. O. is a co-founder of Werewool, a company that is engaged in the development of performance textiles that incorporate engineered proteins. R. S. F. declares no competing interests., (This journal is © The Royal Society of Chemistry.)

Dihedral conformational transitions are analyzed systematically in a model globular protein, cytochrome P450cam, to examine their structural and chemical dependences through combined conventional molecular dynamics (cMD), accelerated molecular dynamics (aMD) and adaptive biasing force (ABF) simulations. The aMD simulations are performed at two acceleration levels, using dihedral and dual boost, respectively. In comparison with cMD, aMD samples protein dihedral transitions approximately two times faster on average using dihedral boost, and ∼ 3.5 times faster using dual boost. In the protein backbone, significantly higher dihedral transition rates are observed in the bend, coil, and turn flexible regions, followed by the β bridge and β sheet, and then the helices. Moreover, protein side chains of greater length exhibit higher transition rates on average in the aMD-enhanced sampling. Side chains of the same length (particularly Nχ = 2) exhibit decreasing transition rates with residues when going from hydrophobic to polar, then charged and aromatic chemical types. The reduction of dihedral transition rates is found to be correlated with increasing energy barriers as identified through ABF free energy calculations. These general trends of dihedral conformational transitions provide important insights into the hierarchical dynamics and complex free energy landscapes of functional proteins.

Rational protein engineering has often focused on increasing the thermal stability of proteins by incorporating stabilising mutations. Introducing fluorinated amino acids into proteins has been used to enhance protein stability. Free energy simulations of the immunoglobulin binding domain of streptococcal protein G in both the folded and unfolded states were performed to understand the detailed mechanism of the effect of fluorinated aromatic and aliphatic amino acid side chains on the stability of Leu → Hfl (hexafluoroleucine) and Phe → Pff (pentafluorophenylalanine) mutations at the solvent-exposed position of the globular protein. Our simulated free energy differences (ΔΔG) for the Leu → Hfl and Phe → Pff mutations are −0.43 ± 0.14 kcal/mol and −0.45 ± 0.20 kcal/mol, respectively. These calculated free energy differences are in excellent agreement with the corresponding reported experimental values. Surprisingly, a significant contribution to the increased stability of the Hfl-containing fluorinated protein comes from van der Waals interactions and, in the case of Pff, electrostatic interactions. The simulated quantitative agreement with experimental values validates the free energy simulation method to elucidate the effect of fluorination on protein stability. The implications of the simulation results for our understanding of the effect of fluorination on protein stability are discussed. [ABSTRACT FROM AUTHOR]

Quite a long time ago, Oleg B. Ptitsyn put forward a hypothesis about the possible functional significance of the molten globule (MG) state for the functioning of proteins. MG is an intermediate between the unfolded and the native state of a protein. Its experimental detection and investigation in a cell are extremely difficult. In the last decades, intensive studies have demonstrated that the MG-like state of some globular proteins arises from either their modifications or interactions with protein partners or other cell components. This review summarizes such reports. In many cases, MG was evidenced to be functionally important. Thus, the MG state is quite common for functional cellular proteins. This supports Ptitsyn’s hypothesis that some globular proteins may switch between two active states, rigid (N) and soft (MG), to work in solution or interact with partners.

Two non-redundant, high-quality sets of protein X-ray crystal structures from the Protein Data Bank (room temperature, 288–298 K, and low temperature, 95–105 K) were compared to structural predictions conducted using ColabFold/AlphaFold2. In particular, the relationship between B-factors and pLDDT values, which estimate the degree of prediction confidence, was investigated. It was observed that there is basically no correlation between these two quantities and, consequently, that the level of confidence in predictions does not provide information about the degree of local structural flexibility of globular proteins.

Albumin is a natural biomaterial that is abundantly available in blood and body fluids. It is clinically used as a plasma expander, thereby increasing the plasma thiol concentration due to its cysteine residues. Albumin is a regulator of intervascular oncotic pressure, serves as an anti-inflammatory modulator, and it has a buffering role due to its histidine imidazole residues. Because of its unique biological and physical properties, albumin has also emerged as a suitable biomaterial for coating implantable devices, for cell and drug delivery, and as a scaffold for tissue engineering and regenerative medicine. As a biomaterial, albumin can be used as surface-modifying film or processed either as cross-linked protein gels or as electrospun fibers. Herein we have discussed how albumin protein can be utilized in regenerative medicine as a hydrogel and as a fibrous mat for a diverse role in successfully delivering drugs, genes, and cells to targeted tissues and organs. The review of prior studies indicated that albumin is a tunable biomaterial from which different types of scaffolds with mechanical properties adjustable for various biomedical applications can be fabricated. Based on the progress made to date, we concluded that albumin-based device coatings, delivery of drugs, genes, and cells are promising strategies in regenerative and personalized medicine.

The temperature dependence of the partial heat capacity of the native protein structure in an aqueous solution has been analyzed. It is shown that the strictly linear temperature dependence is due to the contributions of the vibrational and conformational components, which indicates volume consistensy and the absence of conformational transitions up to the main two-state transition. The two-level structural and functional organization of the protein three-dimensional structure are considered in relation to the energy and conformational entropy properties in accordance with the principles of the organization of the protein macromolecule.Communicated by Ramaswamy H. Sarma.