[AMBER] Question about implicit solvation: DNA-linker conjugate

From: Supriyo Bhattacharya <sup27606.yahoo.com>
Date: Sun, 22 Jul 2018 18:30:07 +0000 (UTC)

Hi everyone,I am trying to simulate the dynamics of a linker conjugated DNA strand using implicit solvation in AMBER. The formula of the molecule I am trying to simulate is:
5'GGTGCATCGATGCAGGGGGG-L-L-L-L-L-C-A-T-T-T-C-C-C-G-T-A-A-A-T-C-L-L                                                                        |    |  |  |  |   |   |   |   |    |  |   |   |   |  |       |                                                      3'-L-L-L-L-G-T-A-A-A-G-G-G-C-A-T-T-T-A-G-L-L
, where L (linker) = -(PO4)-(CH2)-(CH2)-(CH2)-
I have parameterized the linker using Antechamber and assigned am-bcc1 charges. Next I edited the linker prepi file in xleap and specified the head and tail atoms. Finally, I created a frcmod file where I specified the missing parameters (mostly the connections between L and nucleotides) taken from the DNA.bsc1 parameter set. When I performed a test run using igb=8 at 310K, all the phosphate groups in the linker aggregated together immediately and destroyed the DNA double helix. The same system when simulated in explicit water remains stable and does not show aggregation of the phosphates.
Could someone with experience advise what is going wrong with the implicit solvation. Do I need to set any other parameter for the linker phosphates specific to GB solvation (explicit water simulations work fine). Also, the partial charges on the phosphate group are similar if not identical to the DNA phosphates. The missing dihedral parameters for the linker were also taken from equivalent parameters in DNA. I am wondering whether the alpha, beta and gamma parameters of IGB need to be explicitly set for the linker atoms. I thought some default reasonable values are already assigned by AMBER. Please note, I have some prior experience with GB solvent simulations in AMBER, although all of them were with pure protein systems. Could somebody help?
Many thanks in advance,Supriyo
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Received on Sun Jul 22 2018 - 12:00:03 PDT
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