Abstract:
:Human dihydrofolate reductase-like 1 (DHFRL1) has been identified as a second human dihydrofolate reductase (DHFR) enzyme. Although DHFRL1 have high sequence homology with human DHFR, dihydrofolate (DHF) exhibits a lowered binding affinity to DHFRL1 and the corresponding molecular mechanism is still unknown. To address this question, we studied the binding of DHF to DHFRL1 and DHFR by using molecular dynamics simulation. Moreover, to investigate the role the 24th residue of DHFR/DHFRL1 plays in DHF binding, R24W DHFRL1 mutant was also studied. The van der Waals interaction are more crucial for the total DHF binding energies, while the difference between the DHF binding energies of human DHFR and DHFRL1 can be attributed to the electrostatic interaction and the polar desolvation free energy.More specifically, lower DHF affinity to DHFRL1 can be mainly attributed to the reduction of net electrostatic interactions of residues Arg32 and Gln35 of DHFRL1 with DHF as being affected by Arg24. The side chain of Arg24 in DHFRL1 can extend deeply into the binding sites of DHF and NADPH, and disturb the DHF binding by steric effect, which rarely happens in human DHFR and R24W DHFRL1 mutant. Additionally, the conformation of loop I in DHFRL1 was also studied in this work. Interestingly, the loop conformation resemble to normal closed state of Escherichia coli DHFR other than the closed state of human DHFR. We hope this work will be useful to understand the general characteristics of DHFRL1.
journal_name
J Mol Modeljournal_title
Journal of molecular modelingauthors
Gao J,Cui W,Du Y,Ji Mdoi
10.1007/s00894-013-2018-2subject
Has Abstractpub_date
2013-12-01 00:00:00pages
5187-98issue
12eissn
1610-2940issn
0948-5023journal_volume
19pub_type
杂志文章abstract::The increase of multidrug-resistant strains of bacteria to known classes of antibiotics present a severe challenge for modern medicine. The most promising strategy to combat pathogenic bacteria is to discover new drug targets. In this regard, aminoacyl-tRNA synthetases are particularly well suited to develop novel dru...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-008-0421-x
更新日期:2009-06-01 00:00:00
abstract::ORF 3a of human severe acute respiratory syndrome corona virus (SARS-CoV) has been identified as a 274 amino acid membrane protein. When expressed in Xenopus oocytes the protein forms channels. Based on bioinformatics approaches the topology has been identified to include three transmembrane domains (TMDs). Since stru...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-011-1092-6
更新日期:2012-02-01 00:00:00
abstract::Fruit softening is associated to cell wall modifications produced by a set of hydrolytic enzymes and proteins. Expansins are proteins with no catalytic activity, which have been associated with several processes during plant growth and development. A role for expansins has been proposed during softening of fruits, and...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-015-2656-7
更新日期:2015-05-01 00:00:00
abstract::In recent years, it has become clear that the neuronal nicotinic acetylcholine receptor (nAChR) is a valid target in the treatment of a variety of diseases, including Alzheimer's disease, anxiety, and nicotine addiction. As with most membrane proteins, information on the three-dimensional (3D) structure of nAChR is li...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-008-0340-x
更新日期:2008-10-01 00:00:00
abstract::Mechanisms for the activation of water, ammonia, and other small molecules by the PCcarbeneP nickel pincer complex were studied computationally with the aid of density functional theory. The calculation results indicate that the strongly donating, nucleophilic carbene center can engage in a variety of heterolytic spli...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-015-2792-0
更新日期:2015-09-01 00:00:00
abstract::Selective A(2B) receptor antagonists and agonists may play a role in important pathologies such as gastrointestinal, neurological (i.e., Alzheimer disease and dementia) and hypersensitive disorders (i.e., asthma), diabetes, atherosclerosis, restenosis and cancer. Hence, it is regarded as a good target for the developm...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-012-1427-y
更新日期:2012-09-01 00:00:00
abstract::A series of no-chlorine and oxygen-rich hydrazine derivatives (hydrazine modified with -NO₂ and NO₃(-) groups) was designed and optimized to obtain molecular geometries and electronic structures at density functional theory-B3PW91/6-311++G(3df,3pd) level. Some important properties such as bond dissociation enthalpy, d...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-013-1792-1
更新日期:2013-06-01 00:00:00
abstract::Clindamycin, a lincosamide antibiotic, binds to 23S ribosomal RNA and inhibits protein synthesis. The A2058G mutation in 23S RNA results in bacterial resistance to clindamycin. To understand the influence of this mutation on short-range interactions of clindamycin with 23S RNA, we carried out full-atom molecular dynam...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-018-3689-5
更新日期:2018-07-03 00:00:00
abstract::Metallo-β-lactamases (MβLs) can hydrolyze and deactivate lactam-containing antibiotics, which are the major mechanism to cause drug resistance in the treatment of bacterial infections. This has become a global concern due to the lack of clinically approved inhibitors so far. SMB-1 from Serratia marcescents is a novel ...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-020-4330-y
更新日期:2020-03-07 00:00:00
abstract::The geometric and electronic structures, absorption spectra, transporting properties, chemical reactivity indices and electrostatic potentials of the planar three-coordinate organoboron compounds 1-2 and twisted reference compound Mes(3)B, have been investigated by employing density functional theory (DFT) and concept...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-013-1845-5
更新日期:2013-08-01 00:00:00
abstract::The role of resultant gradient-information concept, reflecting the kinetic energy of electrons, in shaping the molecular electronic structure and reactivity preferences of open reactants is examined. This quantum-information descriptor combines contributions due to both the modulus (probability) and phase (current) co...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-019-4028-1
更新日期:2019-08-16 00:00:00
abstract::Human immunodeficiency virus (HIV) infections continue to exert an enormous impact on global human health. This led experts to emphasize the importance of new measures for preventing HIV infections, including the development of vaccines and novel drugs. In this context, a promising approach involves the use of lectins...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-016-3137-3
更新日期:2016-11-01 00:00:00
abstract::Periplasmic binding proteins are the initial receptors for the transport of various substrates over the inner membrane of gram-negative bacteria. The binding proteins are composed of two domains, and the substrate is entrapped between these domains. For several of the binding proteins it has been established that a cl...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-013-1991-9
更新日期:2013-11-01 00:00:00
abstract::The complementarity plot (CP) is an established validation tool for protein structures, applicable to both globular proteins (folding) as well as protein-protein complexes (binding). It computes the shape and electrostatic complementarities (Sm, Em) for amino acid side-chains buried within the protein interior or inte...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-017-3546-y
更新日期:2017-12-07 00:00:00
abstract::The mechanism and regioselectivity of [3+2] cycloaddition (32CA) reactions of benzonitrile oxide with ethyl trans-cinnamate, ethyl crotonate and trans-2-penten-1-ol has been studied in gas phase and in acetonitrile, ethyl acetate and tetrahydrofuran using the B3LYP functional in connection with 6-31G(d) basis set. The...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-020-04547-6
更新日期:2020-09-22 00:00:00
abstract::The adsorption of the molecules CO, CO2, and H2 on several ceria and zinc oxide surfaces was studied by means of periodical DFT calculations and compared with infrared frequency data. The stable CeO2(111), CeO2(331), and ZnO(0001) perfect faces were the first substrates considered. Afterwards, the same surfaces with o...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-014-2270-0
更新日期:2014-06-01 00:00:00
abstract::Abnormal expression of cyclin-dependent kinase 2 (CDK2)/cyclin-E is detected in colorectal, ovarian, breast and prostate cancers. The study of CDK2 with a bound inhibitor revealed CDK2 as a potential therapeutic target for several proliferative diseases. Several highly selective inhibitors of CDK2 are currently underg...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-012-1620-z
更新日期:2013-02-01 00:00:00
abstract::The relationship of Wiener's topochemical index-a distance based topochemical index, molecular connectivity topochemical index-an adjacency based topochemical index and eccentric connectivity topochemical index-an adjacency-cum-distance based topochemical index with sodium channel binding activity has been investigate...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-006-0134-y
更新日期:2007-01-01 00:00:00
abstract::The USFDA has approved pramlintide, commercially named Symlin (sIAPP), as adjunctive therapy for type 2 diabetes (T2D). This analogue of the human amylin peptide (hIAPP) has triple proline substitutions typical of the rat isoform (rIAPP). Recently, it was proposed that pramlintide solubility and aggregation resistance...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-019-4137-x
更新日期:2019-08-19 00:00:00
abstract::Our recent molecular dynamics (MD) simulation of an insertion/duplication mutant 'L20' of bacteriophage T4 lysozyme demonstrated a solvent induced α→β transition in a loosely held duplicate helical region, while α-helical conformation in the parent region was relatively stabilized by its tertiary interactions with the...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-015-2621-5
更新日期:2015-04-01 00:00:00
abstract::A good understanding of the inhibition mechanism of enzymes exhibiting high levels of similarity is the first step to the discovery of new drugs with selective potential. Examples of such proteins include glycogen synthase kinase-3 (GSK-3β) and cyclin-dependent kinase 2 (CDK-2). This article reports the mechanism of s...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-017-3395-8
更新日期:2017-08-01 00:00:00
abstract::A quantum mechanical density functional theory (DFT) was successfully developed for the estimation of pKa values of chlorinated phenols in aqueous solution with a precision of 0.9 pKa units. The MP2/6-311++G(d,p)//B3LYP/6-31+G(d) level of theory was used for the gas phase calculation. For computation in the solution p...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-019-4096-2
更新日期:2019-06-26 00:00:00
abstract::The applicability of the newly developed PM6 method for modeling proteins is investigated. In order to allow the geometries of such large systems to be optimized rapidly, three modifications were made to the conventional semiempirical procedure: the matrix algebra method for solving the self-consistent field (SCF) equ...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-008-0420-y
更新日期:2009-07-01 00:00:00
abstract::Structure-olfactive threshold relationships for 40 pyrazine derivatives have been studied by multivariate statistical analysis. Variable descriptors used to describe the molecules studied were obtained using molecular-mechanics software. A correlation coefficient of 0.82 was obtained when all the molecules were includ...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-006-0115-1
更新日期:2006-09-01 00:00:00
abstract::Cathepsin S has been demonstrated to play a crucial role in the remodeling of extracellular matrix proteins such as elastin and collagen, which in turn contribute to the structural integrity of the cardiovascular wall. Atherosclerotic lesions, aneurysm formation, plaque rupture, thrombosis, and calcification are some ...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-017-3255-6
更新日期:2017-03-01 00:00:00
abstract::APUAMA is a free software designed to determine the reaction rate and thermodynamic properties of chemical species of a reagent system. With data from electronic structure calculations, the APUAMA determine the rate constant with tunneling correction, such as Wigner, Eckart and small curvature, and also, include the r...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-017-3337-5
更新日期:2017-06-01 00:00:00
abstract::We perform density functional theory studies to investigate structural and electronic properties of the (5,5) boron nitride nanotubes (BNNTs) with surfaces and ends functionalized by thiol (SH) and hydroxyl (OH) groups. The exchange-correlation energies are treated according to the functional of Hamprecht-Cohen-Tozer-...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-013-1782-3
更新日期:2013-06-01 00:00:00
abstract::Through the B3LYP/6-311++G(d,p) calculations, theoretical studies of structural parameters, electronic properties, infrared vibration modes, and charge density topologies on the C2H4O∙∙∙HX and C2H5N∙∙∙HX (X = F or O-F) heterocylic hydrogen complexes are presented. The H-bond distances and high energies point out stron...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-015-2829-4
更新日期:2015-11-01 00:00:00
abstract::DFT computations were carried out to characterize the (17)Oand (2)H electric field gradient, EFG, in various bisphosphonate derivatives. The computations were performed at the B3LYP level with 6-311++G (d,P) standard basis set. Calculated EFG tensors were used to determine the (17)O and (2)H nuclear quadrupole couplin...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-011-1114-4
更新日期:2012-03-01 00:00:00
abstract::The treatment of bacterial infections is currently threatened by the emergence of pathogenic bacteria producing β-lactamase, which catalyzes the hydrolysis of β-lactams. Although the hydrolysis of the substrate nitrocefin by a metallo-β-lactamase, namely β-lactamase N1 from USA300 (a typical methicillin-resistant Stap...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-019-4001-z
更新日期:2019-04-13 00:00:00