Unraveling C-Peptide’s Role in MIDY: A Structural Perspective Proinsulin folding requires dynamic positioning of the C-peptide to guide A- and B-chain alignment and disulfide pairing. Mutant INS-gene-induced diabetes of youth (MIDY) arises when single-residue substitutions disrupt this process. We mapped the conformational free-energy landscapes of wild-type (WT) proinsulin and seven MIDY variants using metadynamics and molecular dynamics simulations. WT exhibits a deep free-energy minimum at compact conformations. In contrast, MIDY mutants display a continuum of destabilization: E(A4)K retains near-WT stability, Akita (C(A7)Y), V(B18)A, and R(Cpep + 2)C show moderate loss of the native basin, while H(B5)D, L(A16)P, and Y(B26)C collapse the closed–open barrier and populate misfolded open states >50% of the time. Structural analyses reveal that WT and E(A4)K preserve robust A–C docking, with the C-peptide flexibly engaging the A-chain groove. Destabilizing mutants progressively erode these native A–C contacts while forming compensatory, non-native B–C interactions. Per-residue energy decomposition highlights the loss of canonical salt bridges and emergence of aberrant electrostatic and hydrophobic hot spots, correlating with the collapse of the folding free-energy barrier. Secondary-structure analysis further shows that mutants rigidify the normally disordered C-peptide, increasing helical or strand propensity in a mutation-specific manner. Collectively, these findings establish a continuum from near-native stability to overt misfolding, mechanistically linking single-site mutations to altered folding landscapes and aggregation risk in MIDY. The results highlight the C-peptide as a dynamic linchpin of proinsulin folding and suggest that restoring its flexible docking could provide a therapeutic avenue.

New from our group: Unraveling C-Peptide’s Role in MIDY: A Structural Perspective | ACS Omega pubs.acs.org/doi/10.1021/...

Congratulations @sranga88.bsky.social and my lab folks! 🎉

#proteinfolding #proinsulin #mutations #Cpeptide #structuralbiology #computationalbiology #MDsimulations

A little late: Javier Flores is joining the HiPE group via the CHiPS Act to work on #Semiconductor #AI Modeling and #MolecularDynamics Simulation support. Welcome!

#physics #engineering #deeplearning #mdsimulations #research #txst

Great opportunity to present my work on #MDsimulations of #ORs at #ECRO25, along side many inspiring scientists 🤩

👩🏻‍🏫 Greatful to @tastelabhuji.bsky.social for organizing such an excellent symposium.

🙏🏻 Huge thanks to #LSB and @antonelladipizio.bsky.social for their constant support!!

Structural heterogeneity and dynamics in the apical stem loop of s2m from SARS-CoV-2 Delta by an integrative NMR spectroscopy and MD simulation approach Abstract. In structured RNAs, helical elements are often capped by apical loops that are integral structural elements, ranging from 3 to >20 nts of size

New publication in @narjournal.bsky.social - Using NMR, SAXS & MD, we characterize the dynamic nonaloop of the SARS-CoV-2 Delta s2m RNA, contributing to future ensemble-functional studies of dynamic RNA motifs.

Full text: doi.org/10.1093/nar/...

#RNA #StructuralBiology #NAR #NMR #MDSimulations

Molecular modeling and simulation studies of SELEX-derived high-affinity DNA aptamers to the Ebola virus nucleoprotein Ebola viral disease (EVD) is a highly infectious and potentially fatal illness with a case fatality rate ranging from 25% to 90%. To effectively control its spread, there is a need for rapid, relia...

In Vol 43, Issue 9, In silico MD shows SELEX DNA aptamers bind Ebola NP: Apt1 KD 25 nM > Apt2 56 nM > Apt3 140 nM. Computation mirrors MST, speeding point-of-care EVD tests and showcasing in-silico/in-vitro synergy. #JBSD #MDSimulations www.tandfonline.com/doi/full/10....

Investigating the combined effect of copper, zinc, and iron ions on truncated and full-length Aβ peptides: insights from molecular dynamics simulation The truncated Aβ1 − 16 peptide containing the metal-binding domain is frequently used in in silico and experimental investigations because it is more soluble and thus more suitable for studies in s...

MD simulations show that Cu²⁺ binds strongly to His13/His14 in full-length and truncated Aβ peptides. Zn²⁺ and Fe³⁺ modulate Cu²⁺ binding and reduce aggregation tendency, especially in Aβ₁₋₁₆. Truncation & metal ion synergy shape Aβ structure. #JBSD #MDSimulations www.tandfonline.com/doi/full/10....

Comprehending conformational changes in EmrE, multidrug transporter at different pH: insights from molecular dynamics simulations EmrE is a small multidrug resistance (SMR) pump of antiparallel topology that confers resistance to a broad range of polyaromatic cations in Escherichia coli. Atomic-level understanding of conforma...

From Vol 43, Issue 8 MD simulations show that MGMT mutations alter structure and binding: L84F/K125E mimics wild-type in free form, but L84F alone shows distinct interactions with PCNA/DNA and the highest binding free energy—highlighting SNP-driven conformational shifts. #JBSD #MDSimulations

Congrats to Mitch Turk for defending his MS thesis on "MD SIMULATIONS OF TMAO INTERACTIONS WITH E.COLI 16S RIBOSOMAL RNA" with Dr. Cho! #MDsimulations #Biophysics

Busy week at Wake Physics, especially Thursday. We will start with Mich Turk's MS defense. #MDSimulations #Biophysics

Understanding a point mutation signature D54K in the caspase activation recruitment domain of NOD1 capitulating concerted immunity via atomistic simulation Point mutation D54K in the human N-terminal caspase recruitment domain (CARD) of nucleotide-binding oligomerization domain −1 (NOD1) abrogates an imperative downstream interaction with receptor-int...

Point mutation D54K in the NOD1 CARD domain alters dynamics critical for RIPK2 binding in innate immune signaling. Atomistic MD reveals coil-to-helix transitions and loop distortions that disrupt dimer interface stability. #MDSimulations #JBSD www.tandfonline.com/doi/full/10....

Recognition of human telomeric G-quadruplex DNA by 1,5-disubstituted diethyl-amido anthraquinone derivative in different ion environments causing thermal stabilization and apoptosis Ligand binding to G-quadruplex (G4) structures at human telomeric DNA ends promotes thermal stabilization, disrupting the interaction of the telomerase enzyme, which is found active in 80–85% of ca...

1,5-Disubstituted amido anthraquinone derivative binds human telomeric G-quadruplex DNA, enhancing thermal stability in K⁺ and Na⁺. Biophysical and docking studies reveal groove-binding interactions that shape G4 conformation. #JBSD #MDsimulations www.tandfonline.com/doi/full/10....

Our latest paper just dropped in PNAS! 🎉

Turns out, CRISPR-associated transposons don’t just jump—they dance their way through DNA! 🕺🔬

Exciting times for genome engineering!
🧬 Read more in PNAS: www.pnas.org/doi/10.1073/...

#CRISPR #GeneEditing #PNAS #MDsimulations #CompChem

Comprehending conformational changes in EmrE, multidrug transporter at different pH: insights from molecular dynamics simulations EmrE is a small multidrug resistance (SMR) pump of antiparallel topology that confers resistance to a broad range of polyaromatic cations in Escherichia coli. Atomic-level understanding of conforma...

MD simulations suggest that EmrE undergoes pH-dependent conformational shifts: Glu14/Tyr60 interactions stabilize a closed conformation at high pH, while low pH induces a H3 kink & dual open states. Possible insights into multidrug resistance. #JBSD #MDSimulations www.tandfonline.com/doi/full/10....

Evaluation of substrate specificity and catalytic promiscuity of Bacillus albus cellulase: an insight into in silico proteomic study aiming at enhanced production of renewable energy Cellulases are enzymes that aid in the hydrolysis of cellulosic fibers and have a wide range of industrial uses. In the present in silico study, sequence alignment between cellulases from different...

MD simulations and molecular docking suggest that Bacillus albus cellulase exhibits catalytic promiscuity, with key residues (Phe154, Tyr258, Tyr282, Tyr285, Tyr376) facilitating strong substrate binding. #JBSD #MDsimulations
www.tandfonline.com/doi/full/10....

Deciphering insights into the binding mechanism and plasticity of Telacebec with M. tuberculosis cytochrome bcc-aa3 supercomplex through an unbiased molecular dynamics simulation, free-energy analysis, and DFT study The cytochrome bcc-aa3 supercomplex, a key component in the electron transport chain pathway involved in bacterial energy production and homeostasis, is a clinically validated target for tuberculos...

In Vol 43, Issue 6, 500 ns MD simulations of the Mtb cytochrome bcc-aa3 supercomplex with Telacebec reveal both binding site plasticity and persistent interactions. The binding free energy is driven largely by electrostatics. #JBSD #MDsimulations www.tandfonline.com/doi/full/10....

Molecular dynamics simulations show how antibodies may rescue HIV-1 mutants incapable of infecting host cells High mutation and replication rates of HIV-1 result in the continuous generation of variants, allowing it to adapt to changing host environments. Mutations often have deleterious effects, but varia...

Vol 43:6. MD simulations suggest that antibodies can restore gp41's native 6-helix bundle in HIV-1 mutants. Mutations like Q563R or L565A disrupt secondary structure & domain interactions; binding of F240 or 3D6 re-establishes proper dynamics. #JBSD #MDSimulations www.tandfonline.com/doi/full/10....

Comparative studies of structure and dynamics of caprine, leporine, ovine, and equine serum albumins Serum albumin (SA) is the most prevalent protein found in blood. Human albumin was used as an albumin substitute in hypoalbuminemia pets due to high sequence similarity. SAs from furry animals were...

From Vol 43 Issue 5, MD simulations comparing caprine, leporine, ovine, and equine serum albumins suggest unique structural dynamics driven by domain I differences that may influence drug binding and substitution feasibility. #JBSD #MDsimulations www.tandfonline.com/doi/full/10....

The effect of double (S238F/W159H) mutations on the structure and dynamics of PET degrading enzyme Polyethylene terephthalate (PET) is one of the highly produced synthetic polymers worldwide and had acquired attention due to its impact resistance, high clarity, and light weight. PET has become t...

Next in Vol 43 Issue 3, MD simulations suggest that the S238F/W159H double mutation in IsPETase reconfigures its active site and loop dynamics—potentially boosting substrate binding and catalytic efficiency for PET depolymerization. #MDSimulations #JBSD www.tandfonline.com/doi/full/10....

Inhibition mechanism understanding from molecular dynamics simulation of the interactions between several flavonoids and proton-dependent glucose transporter Proton-dependent glucose transporters as important drug targets can have different protonation states and adjust their conformational state under different pHs. So based on this character, research...

Another interesting use of #MDsimulations on proton‐dependent glucose transporters proposes pH‐driven conformational dynamics. Flavonoid inhibitors bind via hydrophobic interactions in protonated states—unlike non‐inhibitors. #JBSD www.tandfonline.com/doi/full/10....

In-silico characterization of a thermophilic serine protease via homology modeling, docking and molecular dynamics simulations One of the major categories of industrial enzymes, proteases is crucial to the survival of living things. The purpose of this research was to newly thermostable protease from the thermophilum Geoba...

Investigating the thermostable protease Protease JJ through molecular dynamics. RoseTTAFold predicts a subtilisin-like sandwich structure and MD simulations suggest stability at 60–90°C & strong interactions with BSA & β-casein #JBSD #MDsimulations www.tandfonline.com/doi/full/10.... 5/8

We also used #EPR #PELDOR studies and #MDsimulations to propose how protonation affects the conformational ensemble and induces coformational changes allowing the movement of antimicrobial peptides and protons across the #membrane.

#cilia #dynein #cryoET #MDsimulations

MD simulation results showing that the dynein-2 molecule tends to stay on the tyrosinated tubulin lattice compared with the detyrosinated tubulin lattice.

To identify if this is due to the different post-translational modification of the tubulins composing the A- and B-tubules, we performed #MDsimulations. We found that dynein-2 tends to stay on the tyrosinated tubulin lattice compared to the detyrosinated tubulin lattice.
6/8 🧵

MolAR: Memory‐Safe Library for Analysis of MD Simulations Written in Rust MolAR is the first memory-safe library for analysis of MD simulations written in Rust. MolAR is intended to explore the advantages and challenges of implementing molecular analysis software in the me...

#softwarenote #MDsimulations

MolAR: Memory-Safe Library for Analysis of MD Simulations Written in Rust (Yesylevskyy) - J. Comput. Chem.
WileyCTChem: doi.org/10.1002/jcc....

@iocbprague.bsky.social @czechacademy.bsky.social #ReceptorAi

ABE8e: the Beyoncé of base editing—flawless dimerization, exclusive interactions, and unparalleled efficiency! 🎤

Check out our latest work: doi.org/10.1093/nar/...

#CRISPR #BaseEditing #ChemComp #MDsimulations

#research #MDsimulations

Effective Inclusion of Electronic Polarization Improves the Description of Electrostatic Interactions: The #prosECCo75 Biomolecular Force Field (Hector Martinez-Seara) - JCTC: pubs.acs.org/doi/10.1021/...

@iocbprague.bsky.social #vschtpraha #helsinkiuni #VTTFinland

Foldamers controlled by functional triamino acids: structural investigation of α/γ-hybrid oligopeptides - Communications Chemistry Peptide-like foldamers are known to be controlled by amide backbone hydrogen bonding, however, the influence of functional groups forming individual hydrogen-bond networks remains underexplored. Here,...

#research #proteinfolding #foldamers #MDsimulations

Foldamers controlled by functional triamino acids: structural investigation of α/γ-hybrid oligopeptides (Jahn) - CommsChem: doi.org/10.1038/s420...

@iocbprague.bsky.social