Article
Biology
Utsab R. Shrestha, Jeremy C. Smith, Loukas Petridis
Summary: The study demonstrates that enhancing the sampling using Hamiltonian replica exchange molecular simulation (HREMD) leads to accurate unbiased ensembles of intrinsically disordered proteins. Standard molecular simulation cannot reproduce small-angle scattering data as well as HREMD, highlighting the utility of the suggested approach.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ilinka Clerc, Amin Sagar, Alessandro Barducci, Nathalie Sibille, Pau Bernado, Juan Cortes
Summary: Intrinsically disordered proteins and regions play crucial roles in biological processes by performing specialized functions related to the recognition of other biomolecules. Computational approaches have become essential tools for understanding the functional mechanisms of these proteins due to their conformational heterogeneity.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Chemistry, Medicinal
Junxi Mu, Zhengsong Pan, Hai-Feng Chen
Summary: The study found that the interaction of four solvent models (TIP3P, TIP4P-Ew, TIP4P-D, OPC) under ESFF1 can impact the simulation of the radius of gyration (R-g) for IDPs. A new solvent model, TIP4P-B, was developed based on the e parameter to improve the accuracy of R-g simulations. TIP4P-B showed better agreement with experimental observations for both folded proteins and IDPs, while maintaining the advantages of the ESFF1 force field for local structural properties.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biology
Aayush Gupta, Souvik Dey, Alan Hicks, Huan-Xiang Zhou
Summary: This study developed generative autoencoders that can learn from short molecular dynamics simulations and generate full conformational ensembles of intrinsically disordered proteins.
COMMUNICATIONS BIOLOGY
(2022)
Article
Chemistry, Physical
Souvik Dey, Matthew MacAinsh, Huan-Xiang Zhou
Summary: For intrinsically disordered proteins (IDPs), the dynamics of the backbone play a key role in encoding their function. The dynamics are regulated by local interactions, secondary structures, and glycines. These sequence-dependent changes in backbone dynamics allow IDPs to respond to binding partners in a versatile manner.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2022)
Review
Chemistry, Medicinal
Junxi Mu, Hao Liu, Jian Zhang, Ray Luo, Hai-Feng Chen
Summary: Intrinsically disordered proteins (IDPs) play crucial roles in biological processes and are associated with various diseases. Molecular dynamics simulation is a valuable tool for quantifying IDP structures, but faces limitations. Recent force field strategies aim to improve accuracy, but further advancements are needed.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biochemical Research Methods
Moritz Schaeffler, Mohammed Khaled, Birgit Strodel
Summary: The structural heterogeneity and dynamics of intrinsically disordered proteins (IDPs) present a challenge for their characterization solely by experimental techniques. Molecular dynamics simulations offer a powerful complement to experimental approaches. In this study, the construction of transition networks from MD trajectories is demonstrated as a means to reveal the configurational ensemble and structural interconversions of IDPs, using amyloid-beta peptide as an example.
Review
Biochemistry & Molecular Biology
Birgit Strodel
Summary: Although AlphaFold has made breakthroughs in protein structure prediction, it cannot predict protein folding pathways and structures of intrinsically disordered proteins. Molecular dynamics simulations offer an alternative computational method and have successfully explored the energy landscapes of IDP conformational switching and protein aggregation.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Surl-Hee Ahn, Gary A. Huber, J. Andrew McCammon
Summary: Intrinsically disordered proteins (IDPs) have attracted significant attention due to their involvement in biological processes and diseases. Computational studies using Brownian dynamics (BD) simulations with a coarse-grained force field for proteins (COFFDROP) have been conducted to complement experimental work. The researchers found that IDPs' properties, such as hydrodynamic radii and entanglement indices, are influenced by salt concentration.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Medicinal
Cecilia Chavez-Garcia, Jerome Henin, Mikko Karttunen
Summary: This research characterizes the structure and dynamics of MeCP2 protein and provides a computational model that is compatible with experimental data. The study reveals two main conformations of MeCP2 and compares the model with experimental observations.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Xiaochen Cui, Hao Liu, Hai-Feng Chen
Summary: Intrinsically disordered proteins (IDPs) are structurally diverse and play important roles in human diseases. Molecular dynamics simulation complements experimental methods to study IDPs. Current polarizable force fields have limitations in sampling conformers of IDPs. A new polarizable force field, Drude2019IDP, was developed and showed improved performance in reproducing conformers of IDPs.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Eric Fagerberg, Marie Skepo
Summary: Coarse-graining is commonly used to reduce computational cost in simulations, but it is known to have lower transferability and accuracy for systems beyond its parametrization scope. In this study, we compared the performance of a bead-necklace model and a modified Martini 2 model, both coarse-grained models, using a set of intrinsically disordered proteins with different degrees of coarse-graining. The results showed that the naive expectation of the least coarse-grained model performing the best was not true, indicating that a more advanced model is not necessarily better in model choice.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
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
Chemistry, Physical
Florencia Klein, Exequiel E. Barrera, Sergio Pantano
Summary: The CG SIRAH force field shows a good ability to describe the dynamical behavior of IDPs and unstructured peptides, and it can effectively capture the effect of point mutations in loosely structured peptides.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Biochemical Research Methods
Jhullian J. Alston, Andrea Soranno, Alex S. Holehouse
Summary: Over the past two decades, intrinsically disordered proteins and protein regions have been recognized as essential drivers of cellular function, with singlemolecule fluorescence spectroscopy and molecular simulations providing insight into their behavior. When combined, these techniques offer complementary information that can help uncover complex molecular details.
Review
Biochemistry & Molecular Biology
Dmitry Tolmachev, Natalia Lukasheva, Ruslan Ramazanov, Victor Nazarychev, Natalia Borzdun, Igor Volgin, Maria Andreeva, Artyom Glova, Sofia Melnikova, Alexey Dobrovskiy, Steven A. Silber, Sergey Larin, Rafael Maglia de Souza, Mauro Carlos Costa Ribeiro, Sergey Lyulin, Mikko Karttunen
Summary: This review focuses on the computational research of deep eutectic solvents (DESs), describing the technical features of DES simulations and discussing various DES applications. The aim is to demonstrate the current frontiers of computational research of DESs and discuss future perspectives.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Cecilia Chavez-Garcia, Mikko Karttunen
Summary: This study compared the biophysical parameters of triosephosphate isomerases (TIMs) from Trypanosoma cruzi and Trypanosoma brucei using molecular dynamics simulations. The results showed significant differences in the amino acid interactions and hydrogen bond networks between the two proteins. This research provides important insights into the mechanisms underlying the different behaviors of these proteins.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Materials Science, Multidisciplinary
Hossein Ravanbakhsh, Razyeh Behbahani, Hamidreza Yazdani Sarvestani, Elham Kiyani, Meysam Rahmat, Mikko Karttunen, Behnam Ashrafi
Summary: This study evaluates and assists the design of interlocked ceramics under thermal shock loading using finite-element and machine learning methods. The approach successfully finds the optimal designs among over 2 million cases.
ADVANCED ENGINEERING MATERIALS
(2023)
Article
Biophysics
Matthew Davies, A. D. Reyes-Figueroa, Andrey A. Gurtovenko, Daniel Frankel, Mikko Karttunen
Summary: A new method combining mixed radial-angular, three-particle correlation function and unsupervised machine learning was used to investigate the emergence of the ripple phase in DPPC lipid bilayers. Data from atomistic molecular dynamics simulations of varying system sizes were analyzed, revealing four distinct conformational populations of lipids. The presence of ordered, disordered, and splayed tail lipids was observed, with spatial clustering of disordered lipids in the groove side of the ripple phase. Principal component analysis confirmed the existence of the four lipid groups.
BIOPHYSICAL JOURNAL
(2023)
Article
Chemistry, Physical
Dmitry Tolmachev, Victor Nazarychev, Veronika Fedotova, Vitaly Vorobiov, Natalia Lukasheva, Michael Smirnov, Mikko Karttunen
Summary: This study investigates the structure and properties of polymerizable deep eutectic solvents (DESs) based on choline chloride and acrylic acid for 3D printing inks, using multiscale simulations and experiments. The results reveal the physical mechanisms of DES formation and the network-like structure of the mixture with Cl- ions as connecting nodes.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Physics, Multidisciplinary
Razyeh Behbahani, Hamidreza Yazdani Sarvestani, Erfan Fatehi, Elham Kiyani, Behnam Ashrafi, Mikko Karttunen, Meysam Rahmat
Summary: Laser machining is a flexible manufacturing technique that relies on simulation methods and machine learning to optimize processing parameters and reduce experimental costs. These techniques can be applied to a variety of ceramic laser machining processes.
Article
Chemistry, Physical
Nuttawat Sawang, Saree Phongphanphanee, Jirasak Wong-ekkabut, Thana Sutthibutpong
Summary: In this study, a combined analysis procedure involving atomistic molecular dynamics (MD) simulations and network topology was used to investigate the evolutionary consequences on the stability and substrate binding of the main protease enzyme of SARS-CoV2. The analysis revealed the significance of specific mutated residues in affecting the enzyme function and identified an extra binding mode that could facilitate the reaction. This understanding could contribute to the development of drugs against SARS-CoV2 and demonstrates the potential of using MD simulations and network topology analysis as a reverse protein engineering tool.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Engineering, Multidisciplinary
Elham Kiyani, Khemraj Shukla, George Em Karniadakis, Mikko Karttunen
Summary: This article proposes a framework and algorithm for directly uncovering the unknown parts of nonlinear equations from data. By augmenting the original X-PINN method with flux continuity across domain interfaces, the approach demonstrates excellent accuracy in predicting the unknown part of the equation. The results are further validated through symbolic regression to determine the closed form of the equation's unknown part.
COMPUTER METHODS IN APPLIED MECHANICS AND ENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Rohoullah Firouzi, Shahin Sowlati-Hashjin, Cecilia Chavez-Garcia, Mitra Ashouri, Mohammad Hossein Karimi-Jafari, Mikko Karttunen
Summary: The assembly of amyloid-beta peptide (Aβ) into toxic oligomers and fibrils is associated with Alzheimer's disease and dementia. Targeting the monomeric form of Aβ with small molecules or antibodies to disrupt amyloid assembly is a promising therapeutic strategy. This study proposes a computational pipeline, using ensemble docking strategy, to identify catechins' binding sites in monomeric Aβ(42) and explores the crucial interactions for binding. The results suggest that catechins, especially EGCG, can act as potent inhibitors against amyloid aggregation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Carter J. Wilson, Mikko Karttunen, Bert L. de Groot, Vytautas Gapsys
Summary: The stability, solubility, and function of a protein are determined by its net charge and the protonation states of its individual residues. The study demonstrates the applicability of a nonequilibrium alchemical free energy method for accurately predicting pK(a) values, which is comparable to current state-of-the-art predictors. The research also highlights the performance disparity associated with lysine partial charges in certain models and mentions an underused fix for this issue.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Editorial Material
Multidisciplinary Sciences
Vojtech Sadek, Shahin Sowlati-Hashjin, SeyedAbdolreza Sadjadi, Mikko Karttunen, Angel Martin-Pendas, Cina Foroutan-Nejad
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Behnaz Bagheri, Phansiri Boonnoy, Jirasak Wong-ekkabut, Mikko Karttunen
Summary: Oxidized phospholipids have significant effects on the structure and permeability of cell membranes, depending on the degree and concentration of oxidation. Adding PoxnoPC to phospholipid bilayers leads to a reduction in thickness and increased order in the structure, while adding PazePC results in a more significant reduction in thickness and increased disorder. These structural changes enhance the permeability of the bilayers, but the specific effect depends on the type and concentration of the oxidized products.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Physics, Fluids & Plasmas
Mahmood Mazarei, Jan Astrom, Jan Westerholm, Mikko Karttunen
Summary: The universality of interfacial roughness in growing epithelial tissue has been a controversial issue. However, using a simulation model, it is found that the geometric shape of the tissue and the strength of cell-cell adhesion determine the scaling behavior, resolving the controversy.
Article
Physics, Fluids & Plasmas
Elham Kiyani, Steven Silber, Mahdi Kooshkbaghi, Mikko Karttunen
Summary: This paper presents data-driven architectures based on machine learning algorithms for discovering nonlinear equations of motion for phase-field models. The experimental results show that we can effectively learn the time derivatives of the field and use the data-driven partial differential equations (PDEs) to propagate the field in time, achieving results in good agreement with the original PDEs.