Stephen Bergmeier is Associate Professor, Chemistry and Biochemistry at Ohio University. He collaborates with groups across the United States and around the globe on synthetic methods development and Medicinal Chemistry. His research topic is Small Organic Molecule Therapeutics.
"...I have sitting on my desk a shoebox kind of box and it's got little four by six file cards and on each one of these four by six file cards I have a structure drawn and it's got a compound identifier and we have someone's name on there as the person who made the compound and on the various cards there are sort of little pencil marks indicating that we sent so much of it to somebody or we looked at it in a particular assay. And so, you know, actually this is another one of the reasons I really like CDD Vault, is I'm getting rid of my shoeboxes of file cards."
Interviewed by Sylvia Ernst, PhD, Sr. Director Community Growth, Collaborative Drug Discovery, Inc.
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Sylvia
Thank you Stephen for being available to tell us a little bit about your research and how you got to where you are, what you're doing and especially, of course, we are interested to learn more on how you collaborate. But first perhaps you can just tell me a little bit about yourself and your research just and introduce yourself.
Stephen Bergmeier
Okay. Well I'm a professor in the Department of Chemistry and Biochemistry at Ohio University in Athens, Ohio. My research area is synthetic organic, and medicinal chemistry. We do a lot of synthetic methods development chemistry in terms of the very basic research. But out of that has grown a lot of medicinal chemistry. Since we are very much a chemistry group, we do very little, if any, biological chemistry or biochemistry or pharmacology or anything like that within our group. We have to collaborate, if we're going to do anything like that, with people who have expertise in that area.
Sylvia
Interesting. So, how do you collaborate and can you talk a little bit about the type of collaborators? Are they in, let's say, commercial or academia or international or located where you are, and so how do you distribute the work?
Stephen Bergmeier
Well the answer is yes to all of those things. I have a couple of small biotech companies that I collaborate with. One of them is in Athens; the other one is on the other side of the United States. I also collaborate with a variety of other academicians, here at Ohio University but I've also got collaborations going on elsewhere within the United States as well as internationally. So sometimes that is a little bit more of a difficult proposition for us, trying to handle all of the various aspects that a project like this entails doing it both internationally as well as just around the country where you may have a collaborator on the other side of the country and so multiple time zones, et cetera.
Sylvia
So when you say collaborating, what kind of tasks are each lab doing there? It sounds like you do method development or some medicinal chemistry, so is it more the traditional split that some labs do the biological screening for compounds which you synthesize or do you share your work also in other regards?
Stephen Bergmeier
It is very much the traditional approach, I guess I would say, in that we do the design and synthesis of small molecules, and we then ship those off to a biological collaborator somewhere else. It might be here at Ohio University, might be on the other side of the world, but we ship them off and they will look at them in some biological assay or system that they have developed and we hopefully will then get feedback from them and we will then make some new compounds based upon the feedback that we get from them.
Sylvia
And, you mentioned a little bit about like the, you didn't call it challenges, but it sounded like it's sometimes easier to work with people who are really close by then the ones who are further way.
Stephen Bergmeier
Yeah. That's certainly always true.
Sylvia
So can you talk a little bit about what other challenges or what goes easy when you collaborate?
Stephen Bergmeier
Well one of the easy things about collaborating with people at your own University is getting the compounds to our biological collaborator. Along with getting the actual physical compounds, we also have to get information to them regarding structure, stability, and things like that, and then they have to then get information back to us such as: This killed every cell in the well so don't make any more like this sort of thing. Or, oh, it killed every cell in the well so make more like these things. So locally it's really easy. They just simply walk over to our lab. They take the vial with the sample in it back to their lab, and I might see them at lunch or at coffee the next day and they will tell me that, "Oh, yes, we looked at your compound and that looks really nice," or "No, that did not look really nice, but I'll drop off a list of the inhibition," or whatever it was, "when I see you at class, in a faculty meeting tomorrow" or something like that. So those sorts of things are really easy to do. The more challenging aspects, of course, are when you're dealing with someone who is not here at the University. Ohio University is a little bit out of the way so getting other places sometimes takes a little bit longer and so, for example, I have a collaborator at the University of Montana and both of the universities are kind of off the beaten path, if you will, relative to the UPS guy and so next day shipment of a compound is usually a two to three day shipment of a compound. And so we have to be able to plan for that in terms of: Do I need to have that compound stay cold the entire time? And, you know, we've gotten very good at shipping things.
I have a collaborator in Egypt now so not only do we have to deal with shipping compounds to another country, but Egypt is still a little bit unsettled and so getting things through the customs on either end is becoming a little challenging, but we're dealing with that. One of the things I like about CDD actually is that it allows us to simplify some of the things that we normally have to do. So for example, I don't have to ship a hard copy of compound structures as the samples all have a little code on it and then all one has to do is go to CDD and look up the code if we want to look at the structure or anything else like that which is actually really nice for them and for us.
Sylvia
Interesting. So that's a question which I wanted to ask you, too, but since you mentioned it, is there anything else how you use CDD in your collaborations where this is helpful? Is there something you would like to talk about in this regard?
Stephen Bergmeier
Well I guess one of the things that's really nice for both me and collaborators is that oftentimes, they say, "Oh, you know, I read some paper where they were going on and on about this property of molecules being really good for drugs," and they'll say, "Well, can you calculate this property," and I say, "Hey, you don't have to. All you have to do is go to CDD and these properties are actually there so just click on the molecule and you can find, for example, a calculated LogPs, and polar, and surface areas, and things like that. And it helps everybody to sort of look at things like that in terms of what sort of properties are we building in the molecules and it really kind of opens up communication between myself and collaborators that we - that they can say, "Oh, yeah, I was looking at this molecule and it had property X is that important?" And we can talk about various things like that whereas I think previously I certainly would not have done that routinely. Oftentimes, biological collaborators don't always have much interest in the chemical properties of things and so bringing up a chemical property or something like that isn't something I would bring up with them. But now, this information is out there for them and they can simply, looking at it, they can say, oh, well, I saw that the LogP of this thing was three and I was reading in this article that this is really important. Should we be looking at this? And we can have a conversation about it at least. So that's kind of nice.
Sylvia
That's good to know. You're probably using a lot of other technologies as well in your lab and so you pretty much know what you have, what you want. Is there something you have on your wish list what CDD should maybe have but doesn't have for you? Is there something you would wish from us? Are there any other technologies you are using or what do you think you would really like? What would help collaborations even more? You can also say that you're totally happy ;-)
Stephen Bergmeier
I am actually really happy with it. I rarely get any sort of software or anything like that that I'm really happy with just in terms of the molecular modeling aspect of our work. I don't know, you probably don't want to advertise competitors, but we used Spartan and we used some of the Schrödinger things like Glide and stuff like that for docking. And those things can be sometimes difficult to use if you haven't used it in a while. For example, there are definitely aspects to them such that if you don't use them all the time or you haven't used it in awhile, you have a learning curve to figure out how to do things all over again. CDD, I really don't have that issue which I really, really like. It may not have, all sorts of modeling capabilities in there, and I don't know that I really would want to do that because I'm sure it would just increase the complexity and make it harder to use and I wouldn't use it as much. So I'm actually really very happy with it. It has enough stuff that I'm quite happy with it. Actually one thing which always irritates me periodically is that sometimes when you're looking at the molecules you actually have to almost open up the editing window in order to see the structure of the molecule because if you have a big molecule on there it fits it all into the tiny little box that shows up and so it's large. Maybe I need a better monitor, but you can just sort of barely see the details. It's like, yeah, there's a molecule there and I think it must have the structure on there and even when you sort of click on it and you get to the slightly larger one, it's still big enough that you can't really make out a lot of the important details. You actually have to go to the editing window to look at the structure sometimes.
Sylvia
That's good to know, thank you. I will put this on our list. This is how we make progresses is just by listening to our customers. I will definitely bring this forward to our product development. Thank you very much for saying all those nice things about CDD, but I also want to add is you said competitors that's totally fine for us. When you collaborate, you also have to kind of embrace your collaborator and competitor - your “co-optitor”. And that's sometimes an interesting path to walk because in the end we all need each other. I just wanted to share that from my view.
Obviously, you are having really nice active research going. Did you have something like a breakthrough moment or an ah-ha moment in your science or in your work? Is there something sticking out? Something exciting?
Stephen Bergmeier
I don't know that I've really had an “aha moment”. I read articles in various magazines like the Scientist and others like that, or various things online where they talk about their ah-ha moments and I have never really had an ah-ha moment. There are certain things that I look back on and I say, “oh, wow,” that was actually a really good decision to have done that. I think they're more, at least for me, have been more strategic decisions in saying that, I'm not going to pursue this line of research anymore, I'm really going to focus on this other stuff that we're doing because it really does seem to have better potential.
Sylvia
That is interesting. Obviously, decision making is always the hard part and some people have the talent to make better decisions than others. Do you have any advice on how to make good decisions? It seems you have a pretty good track record on that so anything you want to tell the readers or listeners on how to make good decisions?
Stephen Bergmeier
Don't listen to me. No, I've certainly made a number of bad decisions. But I think a lot of it has simply been things that I really found interesting to do and things that I have really found interesting to do have generally worked out. I guess if there's a piece of advice to tell people, it’s the things that you find really interesting, you will make them work out in one way or another because you're going to spend more time on it, you're going to spend more thought on it and it will end up working out. If you have something where you think oh, you know, this is something the grant agency's going to love or this is something which everybody's doing so I can get it published easily, but I'm not really all that keen on it but I think it's a good thing to do, I think you're just not going to work on it in the same way that where you look at a project and you say, “oh, this is really cool” and you're then going to really sit there even if you think that nobody's going to fund this stuff, but you still think it's really cool. I think eventually you get somebody to fund it, people will publish it and things will work out. I guess that's my little bit of advice there if there is any.
Sylvia
That's wonderful advice, that resonates 100% with me. Thank you. That's a real big word of wisdom which usually would be a great moment to close the interview, but I want to ask you, too, whether there is anything else which you would like to share? Something else you would like to say?
Stephen Bergmeier
Actually, one of the things - one of your questions here that you had there before, you asked - how did you manage your data or collaborate? So one of the things we've been doing is going through and getting rid of the way that I used to manage data. I have sitting on my desk a shoebox kind of box and it's got little four by six file cards and on each one of these four by six file cards I have a structure drawn and it's got a compound identifier and we have someone's name on there as the person who made the compound and on the various cards there are sort of little pencil marks indicating that we sent so much of it to somebody or we looked at it in a particular assay. And so, you know, actually this is another one of the reasons I really like CDD, is I'm getting rid of my shoeboxes of file cards.
Sylvia
So you really had a manual process there.
Stephen Bergmeier
Oh, yeah, it was totally manual. We're about half way through the shoebox of putting them into CDD now.
Sylvia
So in your evolution you just jumped over the step of Excel, which is where many people sit for awhile and it's interesting that you took the jump right away into a database and collaborative technology.
Stephen Bergmeier
Well, I never really liked Excel, there was the Chemdraw Excel program but Chemdraw kept changing what they supported or what they didn't support and sometimes it worked well with Excel and sometimes it didn’t. I just really didn't care for upgrading or not upgrading depending upon some software manufacturer’s, schedule. Another reason I like CDD is it's just this web-based product where I don't really need to have a certain computer operating system or need to upgrade whatever operating system I have so that I can continue using it and things like that.
Sylvia
Thank you for pointing that out. That is probably one of the really nice things which I like, too. Not just about CDD but about all the things which appear which are web based now which makes life so easy. So that was very cool talking with you. Thank you, Stephen, for your time.
This blog is authored by members of the CDD Vault community. CDD Vault is a hosted drug discovery informatics platform that securely manages both private and external biological and chemical data. It provides core functionality including chemical registration, structure activity relationship, chemical inventory, and electronic lab notebook capabilities!
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