Binding selectivity of RecA to a single stranded DNA, a computational approach.
Homologous recombination (HR) is the major DNA double strand break repair pathway which maintains the genomic integrity. It is fundamental for the survivability and functionality of all organisms. One of the initial steps in HR is the formation of the nucleoprotein filament composed by a single stranded DNA chain surrounded by the recombinases protein. The filament orchestrates the search for an undamaged homologue, as a template for the repair process. Our theoretical study was aimed at elucidating the selectivity of the interaction between a monomer of the recombinases enzyme in the Escherichia coli, EcRecA, the bacterial homologue of human Rad51, with a series of oligonucleotides of nine bases length. The complex, equilibrated for 20 ns with Langevian dynamics, was inserted in a periodic box with a 8 Å buffer of water molecules explicitly described by the TIP3P model. The absolute binding free energies are calculated in an implicit solvent using the Poisson-Boltzmann (PB) and the generalized Born (GB) solvent accessible surface area, using the MM-PB(GB)SA model. The solute entropic contribution is also calculated by normal mode analysis. The results underline how a significant contribution of the binding free energy is due to the interaction with the Arg196, a critical amino acid for the activity of the enzyme. The study revealed how the binding affinity of EcRecA is significantly higher toward dT₉ rather than dA₉, as expected from the experimental results.
Carra
Claudio
C
Universities Space Research Association, 2101 NASA Parkway, Houston, TX 77058, USA. claudio.carra-1@nasa.gov
Cucinotta
Francis A
FA
D019295:Computational Biology; D004277:DNA, Single-Stranded / Q000737:chemistry*; D029968:Escherichia coli Proteins / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D011938:Rec A Recombinases / Q000737:chemistry*
D004277:DNA, Single-Stranded; D029968:Escherichia coli Proteins; D011938:Rec A Recombinases
Biochim Biophys Acta. 1984 Feb 24;781(1-2):7-13
6365168
Biochemistry. 1985 Jan 29;24(3):760-7
3888263
Biochem Biophys Res Commun. 1988 Nov 30;157(1):127-33
2973785
Annu Rev Biophys Biophys Chem. 1989;18:431-92
2660832
J Biol Chem. 2001 Mar 30;276(13):9613-9
11121401
J Mol Biol. 2003 Jul 18;330(4):891-913
12850155
J Comput Chem. 2002 Jan 15;23(1):15-27
11913381
Biochemistry. 1998 Oct 20;37(42):14788-97
9778353
Proteins. 2004 May 1;55(2):383-94
15048829
Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9068-73
11470894
J Biol Chem. 1998 Oct 30;273(44):28799-804
9786879
J Comput Chem. 2004 Jan 30;25(2):238-50
14648622
J Mol Biol. 1974 Jun 25;86(2):469-89
4416620
Science. 1993 Mar 26;259(5103):1896-9
8456314
J Mol Biol. 1990 Dec 20;216(4):949-64
2266565
J Biomol Struct Dyn. 1998 Dec;16(3):671-82
10052623
J Biol Chem. 2003 Dec 26;278(52):52710-23
14530291
J Biol Chem. 1985 Oct 5;260(22):12308-12
3900072
Science. 1999 Mar 12;283(5408):1676-83
10073925
J Mol Biol. 1999 Mar 5;286(4):1097-106
10047484
Curr Opin Struct Biol. 2001 Jun;11(3):287-92
11406376
J Mol Biol. 1990 Jul 20;214(2):557-70
2380987
Biochemistry. 1990 Aug 21;29(33):7666-76
2148682
J Mol Biol. 1997 Nov 28;274(2):213-21
9398528
J Mol Biol. 2001 Jun 1;309(2):507-17
11371168
Science. 2001 Feb 16;291(5507):1284-9
11181991
Biophys J. 1996 Aug;71(2):670-81
8842206
FEBS J. 2005 Jun;272(11):2734-45
15943808
Protein Sci. 1998 Mar;7(3):649-66
9541397
J Mol Biol. 2005 Mar 4;346(4):1121-45
15701522
J Biol Chem. 1990 May 5;265(13):7351-9
2185246
Eur J Biochem. 1997 May 1;245(3):715-9
9183010
Proteins. 1993 Jul;16(3):226-45
8346190
Biopolymers. 2003 Mar;68(3):333-49
12601793
Biophys J. 2007 Jun 1;92(11):3817-29
17351000
J Biol Chem. 1983 Feb 25;258(4):2586-92
6337158
J Mol Biol. 1988 Dec 20;204(4):959-72
3065521
Crit Rev Biochem Mol Biol. 2007 Jan-Feb;42(1):41-63
17364684
Phys Rev Lett. 2003 May 9;90(18):188101
12786043
Nature. 2006 Oct 19;443(7113):875-8
16988658
Proteins. 1993 Dec;17(4):412-25
8108382
Proteins. 2008 Oct;73(1):134-49
18398905
J Mol Biol. 1992 May 20;225(2):519-32
1593634
Biophys J. 2006 Sep 1;91(5):1941-51
16766620
J Med Chem. 2003 Dec 18;46(26):5628-37
14667217
Science. 1993 Mar 26;259(5103):1892-6
8456313
J Am Chem Soc. 2005 Dec 14;127(49):17253-60
16332074
Nat Rev Cancer. 2008 Jun;8(6):465-72
18451812
J Chem Theory Comput. 2007 Jan 1;3(1):156-169
21072141
Biophys J. 2006 Oct 15;91(8):2798-814
16844742
J Mol Biol. 1992 Sep 5;227(1):334-46
1522597
J Biol Chem. 1981 Aug 25;256(16):8835-44
7021553
Mol Biol (Mosk). 2005 Nov-Dec;39(6):984-98
16358736
J Med Chem. 2000 Oct 5;43(20):3786-91
11020294
Proteins. 2002 Feb 1;46(2):177-89
11807946
J Biomol Struct Dyn. 1996 Feb;13(4):615-25
8906882
Biochimie. 1991 Feb-Mar;73(2-3):191-8
1883881
Biophys J. 2001 Aug;81(2):715-24
11463620
Biochemistry. 1987 Apr 21;26(8):2218-25
3304422
Proteins. 2007 May 1;67(2):418-34
17256770
Biochemistry. 1986 Mar 25;25(6):1226-40
3486003
J Biol Chem. 2000 Apr 14;275(15):10864-9
10753882
J Am Chem Soc. 2002 Apr 24;124(16):4522-34
11960483
J Phys Chem B. 2009 Feb 26;113(8):2234-46
19146384
Protein Sci. 1997 Oct;6(10):2166-79
9336839
Prog Nucleic Acid Res Mol Biol. 1999;63:189-221
10506832
J Mol Biol. 1999 Nov 5;293(4):769-80
10543966
J Mol Biol. 1985 Jan 20;181(2):281-95
3981638
J Chem Theory Comput. 2009 Feb 10;5(2):422-429
19461869
Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):6980-5
12756296
Genes Dev. 1996 Aug 1;10(15):1890-903
8756347
J Med Chem. 2002 Mar 28;45(7):1412-9
11906282
J Biol Chem. 1996 Dec 27;271(52):33515-24
8969216
J Chem Theory Comput. 2006 Mar;2(2):251-8
26626512
Biochemistry. 2006 Nov 14;45(45):13537-42
17087507
Biophys J. 2004 Nov;87(5):3035-49
15339804
Nature. 2008 May 22;453(7194):489-4
18497818
J Mol Biol. 1989 Dec 5;210(3):473-84
2693735
J Mol Biol. 2000 Apr 14;297(5):1145-58
10764579
J Am Chem Soc. 2001 May 2;123(17):3986-94
11457149
J Bacteriol. 1996 Apr;178(7):1881-94
8606161
Cell. 2006 Aug 11;126(3):515-27
16901785
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6264-8
8692803
Proteins. 1991;11(3):205-17
1749773
Q Rev Biophys. 2005 Nov;38(4):405-10
16934172
Proteins. 1995 Sep;23(1):97-110
8539254
Prog Nucleic Acid Res Mol Biol. 1997;56:129-223
9187054
Acc Chem Res. 2002 Jun;35(6):430-7
12069628
Proc Natl Acad Sci U S A. 2004 Jan 13;101(2):511-6
14694192
J Mol Model. 2008 Mar;14(3):201-13
18196298
J Mol Biol. 1993 Dec 5;234(3):554-63
7504735
J Mol Evol. 1997 May;44(5):528-41
9115177
J Mol Biol. 1993 Dec 20;234(4):1207-17
7505336
J Biol Chem. 2005 Apr 8;280(14):13993-4005
15695825
Proteins. 1995 May;22(1):45-54
7675786
Nature. 1992 Jan 23;355(6358):374-6
1731253
Acc Chem Res. 2000 Dec;33(12):889-97
11123888
Annu Rev Biochem. 2002;71:71-100
12045091
J Mol Biol. 1989 Jan 5;205(1):137-47
2926802
Biochemistry. 2006 Sep 12;45(36):10807-14
16953566
Genes Dev. 1998 May 1;12(9):1248-53
9573041
J Biol Chem. 2003 Feb 7;278(6):3545-51
12456687
Angew Chem Int Ed Engl. 2002 Aug 2;41(15):2644-76
12203463
Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11844-9
16877541
Biochemistry. 1982 Nov 23;21(24):6066-72
6758843
J Comput Chem. 2003 Jul 15;24(9):1016-25
12759902
Angew Chem Int Ed Engl. 2003 Jul 7;42(26):2946-74
12851945
J Med Chem. 2000 Nov 2;43(22):4180-8
11063614
Science. 1995 May 26;268(5214):1144-9
7761829