AmberTools

Case, David A.; Aktulga, Hasan Metin; Belfon, Kellon; Cerutti, David S.; Cisneros, G. Andrés; Cruzeiro, Vinícius Wilian D.; Forouzesh, Negin; Giese, Timothy J.; Götz, Andreas W.; Gohlke, Holger; Izadi, Saeed; Kasavajhala, Koushik; Kaymak, Mehmet C.; King, Edward; Kurtzman, Tom; Lee, Tai-Sung; Li, Pengfei; Liu, Jian; Luchko, Tyler; Luo, Ray; Manathunga, Madushanka; Machado, Matias R.; Nguyen, Hai Minh; O’Hearn, Kurt A.; Onufriev, Alexey V.; Pan, Feng; Pantano, Sergio; Qi, Ruxi; Rahnamoun, Ali; Risheh, Ali; Schott-Verdugo, Stephan; Shajan, Akhil; Swails, Jason; Wang, Junmei; Wei, Haixin; Wu, Xiongwu; Wu, Yongxian; Zhang, Shi; Zhao, Shiji; Zhu, Qiang; Cheatham, Thomas E.; Roe, Daniel R.; Roitberg, Adrian; Simmerling, Carlos; York, Darrin M.; Nagan, Maria C.; Merz, Kenneth M.

doi:10.1021/acs.jcim.3c01153

Cited by 271 publications

(209 citation statements)

References 81 publications

(129 reference statements)

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“…The ANM mode that best overlaps with the difference vector of the aligned initial/intermediate and target conformations is selected ( U best ) and the initial conformation is deformed along this vector using a deformation factor (DF: 0.4 Å). Energy minimization is performed for 500 steps and 100 steps of LD simulations are performed with a time step of 0.2 fs at a temperature of 310 K using the Amber 11-Sander 4 biomolecular simulation program(88)(89).…”

Section: Methodsmentioning

confidence: 99%

Computational analysis of long-range allosteric communications in CFTR

Ayca,

Bengi,

Nurit

et al. 2023

Preprint

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Malfunction of the CFTR protein results in cystic fibrosis, one of the most common hereditary diseases. CFTR functions as an anion channel, the gating of which is controlled by long-range allosteric communications. Allostery also has direct bearings on CF treatment: CFTR drugs bind at the periphery of the protein yet affect the gating residues that lie at the center of it. Herein, we combined two computational approaches; Anisotropic Normal Mode-Langevin dynamics (ANM-LD) and Transfer Entropy (TE) and investigated the allosteric communications network of CFTR. The results are in excellent agreement with experimental observations and provide extensive novel insight. We identified residues that serve as pivotal allosteric sources and transducers, many of which correspond to disease causing mutations. We observe that the degenerate and catalytic ATP sites asymmetrically contribute to the allosteric communication, and that the catalytic site provides the greater allosteric input. We demonstrate that drugs that potentiate CFTR's conductance do so not by directly acting on the gating residues, but rather by mimicking the allosteric signal sent by the ATP binding sites. We identify a hitherto unknown allosteric hotspot near the docking site of the phosphorylated R domain, providing a molecular basis for its phosphorylation dependent excitatory role. This study uncovers the molecular basis of allosteric connectivity in CFTR and reveals a novel allosteric hotspot that can serve as a target for the development of novel therapeutics.

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Section: Methodsmentioning

confidence: 99%

Computational analysis of long-range allosteric communications in CFTR

Ayca,

Bengi,

Nurit

et al. 2023

Preprint

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“…The junction region was extended by inserting thymine nucleotides to build n T d3WJ ( n = 0–4). A short energy minimization was applied to repair atomic clashes using the Amber sander program . The minimized structures were solvated with the TIP3P water, Na+ neutralization ions, and additional ions (0.15 M NaCl) using Amber force fields − and Amber LEaP program .…”

Section: Methodsmentioning

confidence: 99%

Design and Characterization of Compact, Programmable, Multistranded Nonimmunostimulatory Nucleic Acid Nanoparticles Suitable for Biomedical Applications

Brumett,

Danai,

Coffman

et al. 2024

Biochemistry

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We report a thorough investigation of the role of single-stranded thymidine (ssT) linkers in the stability and flexibility of minimal, multistranded DNA nanostructures. We systematically explore the impact of varying the number of ssTs in three-way junction motifs (3WJs) on their formation and properties. Through various UV melting experiments and molecular dynamics simulations, we demonstrate that while the number of ssTs minimally affects thermodynamic stability, the increasing ssT regions significantly enhance the structural flexibility of 3WJs. Utilizing this knowledge, we design triangular DNA nanoparticles with varying ssTs, all showing exceptional assembly efficiency except for the 0T triangle. All triangles demonstrate enhanced stability in blood serum and are nonimmunostimulatory and nontoxic in mammalian cell lines. The 4T 3WJ is chosen as the building block for constructing other polygons due to its enhanced flexibility and favorable physicochemical characteristics, making it a versatile choice for creating cost-effective, stable, and functional DNA nanostructures that can be stored in the dehydrated forms while retaining their structures. Our study provides valuable insights into the design and application of nucleic acid nanostructures, emphasizing the importance of understanding stability and flexibility in the realm of nucleic acid nanotechnology. Our findings suggest the intricate connection between these ssTs and the structural adaptability of DNA 3WJs, paving the way for more precise design and engineering of nucleic acid nanosystems suitable for broad biomedical applications.

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“…Amber ff14SB and AM1-BCC force fields were applied to add charges in AmberTools. 45 The grid box size was set to 20 × 20 × 20 Å. The maximum number of binding modes and the maximum energy difference between modes were set to 20 kcal mol −1 and 10 kcal mol −1 , respectively, with an exhaustive global search of 32.…”

Section: Methodsmentioning

confidence: 99%