Article
Biochemistry & Molecular Biology
Monica L. Fernandez-Quintero, Anna Vangone, Johannes R. Loeffler, Clarissa A. Seidler, Guy Georges, Klaus R. Liedl
Summary: Structure-based antibody design and accurate predictions of antibody-antigen interactions are challenging tasks in computational biology. Molecular dynamics simulations reveal that a single static X-ray structure is insufficient to understand the determinants of antibody-antigen recognition. This study investigates antibodies that undergo significant conformational changes upon antigen binding and demonstrates that the paratope states can be utilized to enhance antibody-antigen docking.
Article
Multidisciplinary Sciences
Qiao-Hong Chen, V. V. Krishnan
Summary: This study introduces a rational drug discovery strategy based on intrinsically disordered proteins (IDP), defining a differential binding score (DIBS) to quantitatively determine the binding preferences of ligands to different conformations of IDP. By conducting ensemble docking procedures on repeated sampling of conformations, preferential ligand binding sites of IDP can be determined, making this a valuable screening tool for IDP-based drug discovery.
SCIENTIFIC REPORTS
(2021)
Article
Nanoscience & Nanotechnology
Ruofei Lu, Bingyang Zhao, Li Yang, Shengwu Zheng, Xingjie Zan, Na Li
Summary: Protein-based coatings have attracted immense interest due to their diverse biological functions. By analyzing the water content and pH values, we gain better understanding of the assembly mechanism and properties of protein-based coatings.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Biochemistry & Molecular Biology
Noa Nakata, Ryuichi Okamoto, Tomonari Sumi, Kenichiro Koga, Takeshi Morita, Hiroshi Imamura
Summary: Alcohols and urea have different cosolvent effects on proteins, with TFE acting as a helix stabilizer and urea denaturing helices. Molecular dynamics simulations revealed that the helix stabilization by TFE is due to electrostatic interactions between TFE and side chains, while the coil stabilization by urea is attributed to electrostatic and dispersion interactions between urea and the main chains.
Article
Biochemistry & Molecular Biology
Noa Nakata, Ryuichi Okamoto, Tomonari Sumi, Kenichiro Koga, Takeshi Morita, Hiroshi Imamura
Summary: Alcohols and urea are widely used as protein denaturants due to their properties. 2,2,2-trifluoroethanol (TFE) acts as a helix stabilizer, while urea efficiently denatures ordered native structures. The molecular mechanism behind the cosolvent effects of TFE and urea on protein stability is still controversial.
Article
Biochemistry & Molecular Biology
Louise Laursen, Stefano Gianni, Per Jemth
Summary: This study investigates the folding of a three-domain supramodule from the protein PSD-95, revealing that the PDZ domain folds faster and independently from the SH3-GK tandem. However, concurrent folding of the PDZ domain slows down folding of SH3-GK, resulting in an off-pathway folding intermediate. This contributes to the understanding of multidomain protein folding where individual domains cannot be viewed as separate folding units.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Caitlin Walker, Yingjie Wang, Cristina Olivieri, V. S. Manu, Jiali Gao, David A. Bernlohr, Davide Calebiro, Susan S. Taylor, Gianluigi Veglia
Summary: Somatic mutations in the PRKACA gene lead to the development of Cushing's syndrome, with the E31V allosteric mutation disrupting communication nodes and nucleotide-substrate binding cooperativity. The loss of binding cooperativity in Cushing's syndrome mutants is proportional to the density of the intramolecular allosteric network, suggesting a common mechanism for this disease.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Chemistry, Multidisciplinary
Stefano Gianni, Maria Ines Freiberger, Per Jemth, Diego U. Ferreiro, Peter G. Wolynes, Monika Fuxreiter
Summary: Proteins and their complexes can be described as ensembles that populate an energy landscape, where the diversity arises from the conflicts between interactions shaping the energy landscape. Within this framework, alternative sets of suboptimal contacts can encode specificity without achieving a single structural optimum. The interplay between frustration and fuzziness offers insights into the structural and dynamical continuum of protein assemblies.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Rafayel Petrosyan, Abhishek Narayan, Michael T. Woodside
Summary: Single-molecule force spectroscopy (SMFS) is a powerful tool for studying protein folding dynamics, uncovering energy landscapes of folding, complex folding pathways, mechanisms of chaperones in assisting folding, effects of ribosomes on co-translational folding, and monitoring membrane protein folding.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Applied
Xinyue Yan, Yijia Jia, Hui Man, Shiyan Sun, Yuyang Huang, Baokun Qi, Yang Li
Summary: Tracking the dynamic changes in kidney bean protein isolate (KPI) structure during extreme pH-shifting reveals mechanisms driving unfolding and refolding from a conformational perspective and its relationship with function. Acidic-shifting affects hydrophobic interactions, while alkaline-shifting affects hydrogen bonding and electrostatic interactions. pH-shifting transforms KPI into spherical and rod-like structures, improving its physical and functional properties. pH-shifting treatment expands the application scope of KPI in the food industry.
Article
Chemistry, Medicinal
Michael Souffrant, Xin-Qiu Yao, Donald Hamelberg
Summary: Drug resistance in antiviral treatments is a serious issue in public health. Viral proteins mutate fast, allowing them to escape drugs while still being viable. The mechanism of drug resistance in HIV-1 protease is unclear, but studying conformational ensembles can help detect functional changes.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Physical
Xin-Qiu Yao, Donald Hamelberg
Summary: Conformational dynamics of proteins play a crucial role in their biological processes and functional regulation. This Perspective explores the description of allosteric regulation through protein dynamical responses and introduces alternative computational approaches to map allosteric communication pathways at the atomic level.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Multidisciplinary
Marc Mora, Stephanie Board, Olivier Languin-Cattoen, Laura Masino, Guillaume Stirnemann, Sergi Garcia-Manyes
Summary: Non-native disulfide bonds are dynamic covalent bridges formed in proteins, which can be detected using mechanical force and are associated with protein function and aggregation diseases.
Article
Chemistry, Physical
Yue Sun, Zeshuai Yao, Guangyu Wang, Lisha Wang, Min Bai, Hu Shi
Summary: Zn2+ plays an important role in promoting the aggregation and formation of amyloid plaques. The presence of Zn2+ facilitates the dimerization of Aβ, with stronger binding properties compared to the dimerization of Aβ with zAβ and zAβ with zAβ. Specific residues and the orientation of the imidazole ring's N atom in histidine residues are key factors in these systems. Different driving forces were observed in each system. This study contributes to the understanding of the interaction between Aβ dimers and Zn2+, providing insights into Zn2+-induced nucleation mechanisms.
Article
Engineering, Biomedical
Giuseppe Florio, Nicola M. Pugno, Markus J. Buehler, Giuseppe Puglisi
Summary: The study proposes a simple general framework to predict various aspects of protein structural analyses, focusing on global features of the proteins. The model is demonstrated to be effective in capturing the folding and unfolding behaviors of tropoelastin and its mutations. Additionally, the approach is shown to reproduce important properties of the folding-unfolding mechanical response.
ACTA BIOMATERIALIA
(2021)