Article
Biochemistry & Molecular Biology
Lynn G. Schrag, Xiaorong Liu, Indhujah Thevarajan, Om Prakash, Michal Zolkiewski, Jianhan Chen
Summary: Intrinsically disordered proteins play crucial roles in cell decision making and regulatory networks; cancer-associated mutations in p53-TAD can significantly disrupt the balance of interactions with regulatory proteins; these mutations may modulate the disordered state of p53-TAD to perturb interactions with regulators.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Biology
Antonella Paladino, Luigi Vitagliano, Giuseppe Graziano
Summary: Proteins can adopt either a small number of similar conformations or a large ensemble of flexible conformations to perform their functions. The structural features of proteins are highly influenced by the chemical environment. The molecular mechanisms underlying the effects of chemical denaturants on protein structure are still debated. This review summarizes the main experimental data on protein denaturants and discusses classical and recent interpretations of their molecular basis. It also highlights the impact of denaturants on different types of proteins, such as globular, intrinsically disordered, and amyloid-like assemblies, with a special focus on the importance of intrinsically disordered proteins in physiological processes. The potential role of computational techniques in the future is also discussed.
Article
Biochemistry & Molecular Biology
Xi Wang, Harry M. Greenblatt, Lavi S. Bigman, Binhan Yu, Channing C. Pletka, Yaakov Levy, Junji Iwahara
Summary: This study investigates how D/E repeats cause autoinhibition of HMGB1 and its specific binding to cisplatin-modified DNA. By varying ionic strength, the conformational equilibrium between autoinhibited and uninhibited states can be shifted, revealing fuzzy interactions of D/E repeats with other intrinsically disordered regions. Mutations mimicking post-translational modifications relevant to nuclear export of HMGB1 can moderately modulate DNA-binding affinity, possibly by impacting the autoinhibition.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Valentin Bauer, Boris Schmidtgall, Gergo Gogl, Jozica Dolenc, Judit Osz, Yves Nomine, Camille Kostmann, Alexandra Cousido-Siah, Andre Mitschler, Natacha Rochel, Gilles Trave, Bruno Kieffer, Vladimir Torbeev
Summary: This study utilized a specific amino acid substitution pattern to modify the free activation domain of transcriptional coactivator ACTR, resulting in increased binding affinity to CREB-binding protein. The X-ray structure of the modified ACTR domain - NCBD complex revealed a unique conformation of ACTR, demonstrating a strategy for characterizing individual conformational states of IDPs.
Article
Multidisciplinary Sciences
Rajkama, Nisal, P. Jitendra, Agata, Susan, Geoff, W. Aaron, J. Anita, Namita Roy, K. Naba
Summary: This study reveals the impact of crowding on the dynamic conformation of intrinsically disordered proteins (IDPs). Through experimental methods and model construction, researchers found that crowding can induce specific conformational changes in IDPs. This study is of great importance for a better understanding of the interactions and structural dynamics of IDPs in crowded environments.
Article
Biochemistry & Molecular Biology
Christopher J. Brown, Chandra S. Verma, David P. Lane, Dilraj Lama
Summary: A study was conducted to develop peptide derivatives from intrinsically disordered eIF4G scaffold through molecular dynamics simulations and biophysical assays for regulating eIF4E protein interactions. Insights into the differential binding affinities of these peptides and the rate-limiting Y4: P38 hydrogen-bond interaction between the peptide and eIF4E were key findings. These insights were used to design features into the peptide to generate a potent eIF4E binder for potential therapeutic interventions in oncology.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Chemistry, Physical
Wenning Wang
Summary: Recent progress in atomic MD simulation studies of intrinsically disordered proteins (IDPs) includes the development of force fields and sampling methods, as well as applications in IDP-involved protein-protein interactions. Large-scale simulations and advanced sampling techniques allow for a more accurate estimation of the thermodynamics and kinetics of IDP-mediated protein interactions. The holistic landscape of the binding process of IDPs is emerging through these simulations.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Nicolas Palopoli, Julia Marchetti, Alexander M. Monzon, Diego J. Zea, Silvio C. E. Tosatto, Maria S. Fornasari, Gustavo Parisi
Summary: This study reveals that intrinsically disordered proteins (IDPs) evolve under strong site-specific evolutionary rate heterogeneity, mainly due to different constraints from their inter-residue contacts. Evolutionary rate profiles correlate with the experimentally observed conformational diversity, allowing the description of different conformational patterns possibly related to their structure-function relationships.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sreemantee Sen, Harish Kumar, Jayant B. Udgaonkar
Summary: Tau protein fragment tau-K18 undergoes a disorder to order transition in the presence of lipid micelles and vesicles, forming helical structures induced by a phospholipid mimetic. It has been shown that the mechanism of helical structure formation involves an intermediate state I, which can further progress to form a final helical state with a time constant of 50-200 microseconds. The helical conformation is found to be an aggregation-competent state that can lead to the formation of amyloid fibrils.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Thinh D. N. Luong, Suhani Nagpal, Mourad Sadqi, Victor Munoz
Summary: This article introduces a method called "Molecular LEGO" that allows for the dissection of conformational landscapes of unbound intrinsically disordered proteins (IDPs) and provides insights into the functional mechanisms of these proteins. The method was applied to the protein NCBD and revealed specific energetic biases and conformational rheostatic behavior in NCBD's folding landscape, which are likely crucial for its function as a transcriptional coactivator.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Mona Koder Hamid, Linda K. Mansson, Viktoriia Meklesh, Per Persson, Marie Skepo
Summary: This study investigates the structural changes of an intrinsically disordered protein (IDP) when it adsorbs to a solid surface. Molecular dynamics simulations and experimental results were used to compare and analyze the changes. The study found that adsorption increases the helical content and polyproline II helices of the protein, and extends its conformation. Simulations B, E, and G showed better agreement with experimental results than other simulations.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Greta Bianchi, Marco Mangiagalli, Alberto Barbiroli, Sonia Longhi, Rita Grandori, Carlo Santambrogio, Stefania Brocca
Summary: This study investigates the effects of charge patterning on the average compactness and shape of three model IDPs with different proline content. The results show that charge clustering induces remodeling of the conformational ensemble, promoting compaction and/or increasing spherical shape. Additionally, the shape and volume of the ensembles depend on other factors such as charge distribution.
Article
Chemistry, Multidisciplinary
Samuel Naudi-Fabra, Maud Tengo, Malene Ringkjobing Jensen, Martin Blackledge, Sigrid Milles
Summary: Studying the conformational landscape of intrinsically disordered and partially folded proteins is challenging and requires an integrated approach using multiple techniques to accurately describe the conformational ensembles of these proteins. This integrated approach has been successfully tested and validated, providing new insights into the conformational landscape of viral proteins and demonstrating its potential for integrative dynamic structural biology.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biology
Sophia Manukian, Gerrick E. Lindberg, Emily Punch, Sudarshi Premawardhana Dassanayake Mudiyanselage, Matthew J. Gage
Summary: The importance of pH shifts in biological systems is often overlooked. This study investigates the impact of non-ionizable residues on the pH sensitivity of the poly-E motif of muscle protein titin. The results highlight the influence of aromatic amino acids and proline residues on the conformational flexibility of this region.
Article
Biochemistry & Molecular Biology
Katharina Laass, Felipe Garcia Quiroz, Johannes Hunold, Stefan Roberts, Ashutosh Chilkoti, Dariush Hinderberger
Summary: The study reveals the hydration dynamics in phase-separating IDPs, showing that side-chain rehydration forms a dynamic water shield that affects solubility. This water shell strength is a sequence feature of IDPs, encoding for the stability of their phase-separated assemblies. The complexity of nanoscopic water-IDP interactions dictates their rich phase separation behavior.
Article
Materials Science, Composites
Siyuan He, Tiffany R. Walsh
Summary: Carbon-fibre reinforced polymer composites are important in various industries due to their light weight and strong mechanical performance, with the interface between the resin matrix and carbon fiber surface being a critical zone. Molecular simulations are crucial for studying structure/property relationships at this interface, especially in the case of vinyl ester resin interfaces which have been relatively under-explored. Results from simulating the polymerization of vinyl ester/styrene resin near a pristine fiber surface showed poor interfacial integrity, indicating the need for further exploration of surface functionalization strategies for vinyl ester resin carbon fiber composites.
COMPOSITES SCIENCE AND TECHNOLOGY
(2022)
Article
Chemistry, Physical
Alexander J. Marsden, Mark Skilbeck, Matthew Healey, Helen R. Thomas, Marc Walker, Rachel S. Edwards, Natalya A. Garcia, Filip Vukovic, Hicham Jabraoui, Tiffany R. Walsh, Jonathan P. Rourke, Neil R. Wilson
Summary: This article investigates the structural traits of graphene oxide (GO) and their impact on properties. Through experimental approaches and molecular simulations, it is found that extended topological defects are common in GO and greatly influence its properties. The presence of these defects plays a crucial role in the retention of oxygen functional groups after reduction, and GO displays lower strength and stiffness compared to graphene.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Polymer Science
Kenee Kaiser S. Custodio, Tiffany R. Walsh
Summary: This study used molecular simulations to explore the structure/property relationships of phosphorus-containing bio-based resins, uncovering the crucial role of the pendant phosphite group in maintaining mechanical properties. The findings provide a foundation for knowledge-based strategies to systematically improve the structure/property relationships in flame retardant bio-based epoxy resins.
JOURNAL OF POLYMER SCIENCE
(2022)
Article
Chemistry, Medicinal
Yuxiang Wang, Alper Kiziltas, Patrick Blanchard, Tiffany R. Walsh
Summary: This article introduces a flexible and automated contact angle estimation tool, ContactAngleCalculator, which accurately estimates the contact angle in molecular simulations using coarse-graining technique and the concept of equivalent contact area and volume of the droplet. This tool can be integrated with machine learning methods to substantially streamline and reduce human labor and time in computational contact angle estimation.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Multidisciplinary
Ruitao Jin, Tiffany R. Walsh
Summary: This study completes the interfacial adsorption free energy dataset for all 20 amino acids and a range of tripeptides using enhanced sampling techniques. Based on this dataset, a reductionist approach is proposed to design new dodecapeptides with stronger binding to h-BN. The results indicate increased surface contact for the designed BP7-derived sequences.
ADVANCED MATERIALS INTERFACES
(2022)
Article
Nanoscience & Nanotechnology
Siyuan He, Tiffany R. Walsh
Summary: Surface functionalization using covalently grafted molecules has successfully enhanced the interfacial integrity of epoxy-based composites. However, there are limitations in applying this strategy to composite resins based on chain-growth polymerization mechanisms. This study introduces a concept based on short, surface-grown polymers to systematically enhance and tailor the interfacial mechanical properties of these composites, providing practical guidance for optimizing the interface and expanding their applications.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Materials Science, Multidisciplinary
Le Nhan Pham, Tiffany R. Walsh
Summary: This study introduces a molecular dynamics simulation strategy to predict the structures and properties of diblock copolymers used to coat the surface of upconversion nanoparticles. By modeling their interactions with water, the optimal polymer size is identified, which has significant implications for the bioconjugation efficiency of the coated nanoparticles.
ACS APPLIED POLYMER MATERIALS
(2022)
Article
Materials Science, Multidisciplinary
Natalya A. Garcia, Joel B. Awuah, Chaoyue Zhao, Filip Vukovic, Tiffany R. Walsh
Summary: In this study, a modular tiling concept and the HierGO code suite were introduced to automatically generate highly complex models of GO with control over holes, topological defects, and oxygen group placement. The simulations using these models provided new insights into the structure/property relationships of GO membranes and their permeation pathways for water, ions, and molecular agents under different processing conditions.
Article
Chemistry, Physical
Sherif Abdulkader Tawfik, Mahad Rashid, Sunil Gupta, Salvy P. Russo, Tiffany R. Walsh, Svetha Venkatesh
Summary: A machine learning classifier is trained using a dataset of vibrational stability to accurately distinguish between vibrationally stable and unstable materials, which has the potential to be a crucial filtering tool for online material databases, informing the material science community about the vibrational stability or instability of the materials queried in convex hulls.
NPJ COMPUTATIONAL MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Sydney C. Brooks, Ruitao Jin, Victoria C. Zerbach, Yuyu Zhang, Tiffany R. Walsh, Nathaniel L. Rosi
Summary: Assembling nanoparticles into well-defined superstructures with emergent properties depends on their 3-D structural arrangement. Peptide conjugate molecules that bind to NP surfaces and direct NP assembly have been useful, and modifications to these conjugates have observable effects on nanoscale structure and properties. This study explored how changes in the ninth amino acid residue affect the structure of helical assemblies, and found that decreased affinity to the surface led to a transition from double helices to single helices, accompanied by a plasmonic chiroptical signal. The findings demonstrate the ability to precisely control inorganic NP structure and assembly through modifications to peptide precursors.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Garima S. Dobhal, Le Nhan Pham, Sherif Abdulkader Tawfik, Cristina Pozo-Gonzalo, Tiffany R. Walsh
Summary: The addition of water to ionic liquid can induce structural changes in Nd3+-TFSI- complexes, leading to enhanced electrochemical deposition of neodymium. Energetic analyses of these structural changes can explain the observed water-loading effects.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2023)
Article
Chemistry, Multidisciplinary
Sydney C. Brooks, Ruitao Jin, Victoria C. Zerbach, Yuyu Zhang, Tiffany R. Walsh, Nathaniel L. Rosi
Summary: The study examines the effects of the ninth amino acid residue (M) variation on the structure of helical gold nanoparticle assemblies. Different peptide conjugates with varying gold binding affinities were designed and their binding scores were determined through molecular dynamics simulations. It was observed that a structural transition from double helices to single helices occurs as the peptide's binding affinity to the gold surface decreases, accompanied by the emergence of a plasmonic chiroptical signal. The simulations were also used to predict new peptide conjugates that can preferentially direct the formation of single-helical gold nanoparticle superstructures.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Ruitao Jin, Nermina Brljak, Robert Sangrigoli, Tiffany R. Walsh, Marc R. Knecht
Summary: By integrating different materials-binding domains and harnessing biological recognition, the designed BEAM molecule is capable of achieving regiospecific binding to graphene and h-BN surfaces, showing potential in guiding material self-organization in aqueous media.
Article
Materials Science, Biomaterials
Yuliana Perdomo, Ruitao Jin, Atul D. Parab, Marc R. Knecht, Tiffany R. Walsh
Summary: The non-destructive functionalization of graphene in aqueous media using peptides has the potential to enhance its versatility and expand its applications in bio-related fields. This study investigates the binding affinity and adsorbed structures of bio-conjugates consisting of a graphene-binding peptide and a fatty acid chain of varying length at the aqueous graphene interface. The findings provide a solid foundation for designing multi-functional bio-interfaces for sensing and healthcare.
JOURNAL OF MATERIALS CHEMISTRY B
(2022)
Article
Chemistry, Multidisciplinary
Le Nhan Pham, Tiffany R. Walsh
Summary: A new force field, MoSu-CHARMM, has been developed to describe the bio-interfacial structures at the aqueous MoS2 interface based on quantum chemical data. This force field accurately represents the non-covalent interactions between the MoS2 surface and various chemistries. Its performance has been validated against experimental data, making it a valuable tool for large-scale simulations of biological interactions with MoS2 surfaces.