Publications with Fulltext
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
Browse
5 results
Search Results
Publication Open Access Mechanistic differences of activation of Rac1(P29S) and Rac1(A159V)(American Chemical Society (ACS), 2021) Jang, Hyunbum; Nussinov, Ruth; N/A; Department of Chemical and Biological Engineering; Department of Computer Engineering; Şenyüz, Simge; Keskin, Özlem; Gürsoy, Attila; Faculty Member; Department of Chemical and Biological Engineering; Department of Computer Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; 26605; 8745Rac1 is a small GTPase that plays key roles in actin reorganization, cell motility, and cell survival/growth as well as in various cancer types and neurodegenerative diseases. Similar to other Ras superfamily GTPases, Rac1 switches between active GTP-bound and inactive GDP-bound states. Switch I and II regions open and close during GDP/GTP exchange. P29S and A159V (paralogous to K-Ras(A146)) mutations are the two most common somatic mutations of Rac1. Rac1(P2)(9S)( )is a known hotspot for melanoma, whereas Rac1(A159V) most commonly occurs in head and neck cancer. To investigate how these substitutions induce the Rac1 dynamics, we used atomistic molecular dynamics simulations on the wild-type Rac1 and two mutant systems (P29S and A159V) in the GTP bound state, and on the wild-type Rac1 and P29S mutated system in the GDP bound state. Here, we show that P29S and A159V mutations activate Rac1 with different mechanisms. In Rac1(P29S)-GTP, the substitution increases the flexibility of Switch I based on RMSF and dihedral angle calculations and leads to an open conformation. We propose that the open Switch I conformation is one of the underlying reasons for rapid GDP/GTP exchange of Rac1(P29S). On the other hand, in Rac1(A159V)-GTP, some of the contacts of the guanosine ring of GTP with Rac1 are temporarily lost, enabling the guanosine ring to move toward Switch I and subsequently close the switch. Rac1(A159V)-GTP adopts a Ras state 2 like conformation, where both switch regions are in closed conformation and Thr35 forms a hydrogen bond with the nucleotide.Publication Open Access Effect of methylation of ionic liquids on the gas separation performance of ionic liquid/metal-organic framework composites(Royal Society of Chemistry (RSC), 2018) Department of Chemical and Biological Engineering; Nozari, Vahid; Keskin, Seda; Uzun, Alper; Zeeshan, Muhammad; Faculty Member; PhD Student; Department of Chemical and Biological Engineering; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Koç University Tüpraş Energy Center (KUTEM) / Koç Üniversitesi Tüpraş Enerji Merkezi (KÜTEM); Graduate School of Sciences and Engineering; N/A; 40548; 59917; N/A1-N-Butyl-3-methylimidazolium hexafluorophosphate, [BMIM]ijPF6], and its methylated form, 1-N-butyl2,3-dimethylimidazolium hexafluorophosphate, [BMMIM]ijPF6], were incorporated into CuBTC to examine the effect of methylation of ionic liquids (ILs) on the gas separation performance of the corresponding IL/ metal–organic framework (MOF) composites. Spectroscopic analysis revealed that the interactions of the methylated ILs with CuBTC were weaker compared to those of its non-methylated counterpart. Gas uptake measurements illustrated that this difference in the interactions influences the gas separation performance of the composites. Accordingly, the CO2/N2: 15/85 and CH4/N2: 50/50 selectivities increased by 37% and 60% for [BMMIM]ijPF6]/CuBTC and 34% and 50% for [BMIM]ijPF6]/CuBTC, respectively, compared to the corresponding selectivities of pristine CuBTC at 1000 mbar. The results revealed another structural parameter controlling the performance of the IL/MOF composites, a novel type of material with rapidly expanding application areas.Publication Open Access Doping-induced isotopic (MgB2)-B-11 bulk superconductor for fusion application(Multidisciplinary Digital Publishing Institute (MDPI), 2017) Cai, Qi; Guo, Qianying; Liu, Yongchang; Ma, Zongqing; Li, Huijun; Qiu, Wenbin; Patel, Dipak; Jie, Hyunseock; Kim, Jung Ho; Yanmaz, Ekrem; Devred, Arnaud; Luzin, Vladimir; Fatehmulla, Amanullah; Farooq, Wazirzada Aslam; Gajda, Daniel; Bando, Yoshio; Yamauchi, Yusuke; Pradhan, Subrata; Hossain, Md. Shahriar A.; Department of Chemistry; Somer, Mehmet Suat; Faculty Member; Department of Chemistry; College of Sciences; 178882Superconducting wires are widely used for fabricating magnetic coils in fusion reactors. Superconducting magnet system represents a key determinant of the thermal efficiency and the construction/operating costs of such a reactor. In consideration of the stability of B-11 against fast neutron irradiation and its lower induced radioactivation properties, MgB2 superconductor with B-11 serving as the boron source is an alternative candidate for use in fusion reactors with a severe high neutron flux environment. In the present work, the glycine-doped (MgB2)-B-11 bulk superconductor was synthesized from isotopic B-11 powder to enhance the high field properties. The critical current density was enhanced (10(3) Acm(-2) at 20 K and 5 T) over the entire field in contrast with the sample prepared from natural boron.Publication Open Access Normal mode analysis of KRas4B reveals partner specific dynamics(American Chemical Society (ACS), 2021) Jang, Hyunbum; Nussinov, Ruth; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Department of Computer Engineering; Tunçbağ, Nurcan; Gürsoy, Attila; Keskin, Özlem; Eren, Meryem; Faculty Member; Faculty Member; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Department of Computer Engineering; School of Medicine; College of Engineering; Graduate School of Sciences and Engineering; 245513; 8745; 26605; N/ARas GTPase interacts with its regulators and downstream effectors for its critical function in cellular signaling. Targeting the disrupted mechanisms in Ras-related human cancers requires understanding the distinct dynamics of these protein-protein interactions. We performed normal mode analysis (NMA) of KRas4B in wild-type or mutant monomeric and neurofibromin-1 (NF1), Son of Sevenless 1 (SOS1) or Raf-1 bound dimeric conformational states to reveal partner-specific dynamics of the protein. Gaussian network model (GNM) analysis showed that the known KRas4B lobes further partition into subdomains upon binding to its partners. Furthermore, KRas4B interactions with different partners suppress the flexibility in not only their binding sites but also distant residues in the allosteric lobe in a partner-specific way. The conformational changes can be driven by intrinsic residue fluctuations of the open state KRas4B-GDP, as we illustrated with anisotropic network model (ANM) analysis. The allosteric paths connecting the nucleotide binding residues to the allosteric site at alpha 3-L7 portray differences in the inactive and active states. These findings help in understanding the partner-specific KRas4B dynamics, which could be utilized for therapeutic targeting.Publication Open Access Collisional relaxation kinetics for ortho and para NH2- under photodetachment in cold ion traps(Royal Society of Chemistry (RSC), 2018) Gianturco, Francesco A.; Lakhmanskaya, Olga Y.; Vera, Mario Hernandez; Wester, Roland; Department of Chemistry; Yurtsever, İsmail Ersin; Faculty Member; Department of Chemistry; College of Sciences; 7129The collisional cooling of the internal rotational states of the nonlinear anion NH2- ((1)A(1)), occurring at the low temperature of a cold ion trap under helium buffer gas cooling, is examined via quantum dynamics calculations and ion decay rate measurements. The calculations employ a novel ab initio potential energy surface that describes the interaction anisotropy and range of action between the molecular anions and the neutral He atoms. The state changing integral cross sections are employed to obtain the state-to-state rate coefficients, separately for the ortho- and the para-NH2- ions. These rates are in turn used to compute the state population evolution in the trap for both species, once photodetachment by a laser is initiated in the trap. The present work shows results for the combined losses of both species after the photodetachment laser is switched on and analyzes the differences of loss kinetics between the two hyperfine isomers.